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Singh S, Sharma P, Mahant S, Das K, Som A, Das R. Analysis of Functional Status of Genetically Diverse OipA Gene in Indian Patients with Distinct Gastrointestinal Disease. Curr Microbiol 2022; 80:35. [PMID: 36512098 DOI: 10.1007/s00284-022-03137-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori (H. pylori,) a genetically diversified bacteria which colonizes human gastric epithelium, is now established causative agent for gastric cancer worldwide. Outer membrane protein (OMP)-coding genes of H. pylori are responsible for attachment and colonization of bacteria. These genes which code proteins on outer membrane of H. pylori is a group of 33 genes which with other virulent genes are causative of giving rise to disease-causing factors in the host. OipA (Outer inflammatory protein A), a participant of Hop family of OMP, is effective in acting as a biomarker for studying progression of diseases like gastric cancer. The functionality of oipA gene is regulated by phase variation within CT repeat pattern. It is the expression, i.e., "on"/"off" of oipA gene which is related with the development of distinct gastric diseases. 40 amplified DNA sequences were studied to investigate functional status of oipA. Our results reveal 57.2% isolates with functional oipA along with significant association with cagA (P = 0.0011) and vacAs1m1/s1m2 (P = 0.0034, P = 0.0093) genotypes, respectively. In conclusion, our results indicate diversity in CT repeat pattern among Indian H. pylori strains. The prevalence of functional oipA gene was found to be ranging between 50% and 64.2% though it did not show significant correlation between functional oipA and disease outcome.
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Affiliation(s)
- Sarika Singh
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, UP, India
| | - Prateek Sharma
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, UP, India
| | - Shweta Mahant
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, UP, India
| | - Kunal Das
- Department of Gastroenterology, Yashoda Superspeciality Hospital, Ghaziabad, UP, India
| | - Anup Som
- Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj, 211002, UP, India
| | - Rajashree Das
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, UP, India.
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Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol 2022; 13:1347-1363. [PMID: 35124288 PMCID: PMC8933844 DOI: 10.1016/j.jcmgh.2022.01.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 12/30/2022]
Abstract
Gastric cancer (GC) is the fifth most common cancer and the fourth most common cause of cancer-related death worldwide. The intestinal type of GC progresses from acute to chronic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma. Infection of the stomach by Helicobacter pylori, a Gram-negative bacterium that infects approximately 50% of the world's population, is the causal determinant that initiates the gastric inflammation and then disease progression. In this context, the induction of the innate immune response of gastric epithelial cells and myeloid cells by H. pylori effectors plays a critical role in the outcome of the infection. However, only 1% to 3% of infected patients develop gastric adenocarcinoma, emphasizing that other mechanisms regulate the localized non-specific response, including the gastric microbiota and genetic factors. This review summarizes studies describing the factors that induce and regulate the mucosal innate immune response during H. pylori infection.
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Affiliation(s)
- Alain P Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee.
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
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Lenti MV, Rugge M, Lahner E, Miceli E, Toh BH, Genta RM, De Block C, Hershko C, Di Sabatino A. Autoimmune gastritis. Nat Rev Dis Primers 2020; 6:56. [PMID: 32647173 DOI: 10.1038/s41572-020-0187-8] [Citation(s) in RCA: 199] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/26/2020] [Indexed: 02/07/2023]
Abstract
Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to the loss of intrinsic factor and reduced acid output. These alterations result in malabsorption of iron, vitamin B12 (pernicious anaemia) and potentially other micronutrients. For several years, most studies have focused on pernicious anaemia only, generating confusion between the two entities. In AIG, the gastric proton pump, H+/K+ ATPase, is the major autoantigen recognized by autoreactive T cells. The T cell-dependent activation of B cells stimulates the production of anti-parietal cell antibodies, the serological hallmark of AIG. The role of Helicobacter pylori infection in activating or favouring the autoimmune process is still uncertain. Early histopathological alterations allowing a more precise and prompt recognition have recently been described. AIG is burdened by a substantial diagnostic delay as it can present with varied clinical signs including, among others, gastrointestinal symptoms and neuropsychiatric manifestations. In advanced stages, AIG might progress to neuroendocrine tumours and gastric adenocarcinoma. Management includes early detection through a proactive case-finding strategy, micronutrient supplementation and endoscopic surveillance. This Primer comprehensively describes the most important insights regarding the epidemiology, pathophysiology, diagnosis and management of AIG, focusing on the most controversial, outstanding issues and future directions.
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Affiliation(s)
- Marco Vincenzo Lenti
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Edith Lahner
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Emanuela Miceli
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Ban-Hock Toh
- Centre for Inflammatory Diseases, Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
| | - Robert M Genta
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA
| | - Christophe De Block
- Department of Endocrinology, Diabetology and Metabolism, Faculty of Medicine, Antwerp University Hospital and University of Antwerp, Antwerpen, Belgium
| | - Chaim Hershko
- Department of Hematology, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.,Hematology Clinic and Central Clinical Laboratories, Clalit Health Services, Jerusalem, Israel
| | - Antonio Di Sabatino
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
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Kpoghomou MA, Wang J, Wang T, Jin G. Association of Helicobacter pylori babA2 gene and gastric cancer risk: a meta-analysis. BMC Cancer 2020; 20:465. [PMID: 32448131 PMCID: PMC7247142 DOI: 10.1186/s12885-020-06962-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 05/13/2020] [Indexed: 01/06/2023] Open
Abstract
Background The association of Helicobacter pylori (H. pylori) babA2 gene with gastric cancer (GC) was reported by several studies, but results were inconsistent. This meta-analysis was performed to investigate the relationship between H. pylori babA2 gene and GC risk. Methods Case-control studies involving the association between H. pylori babA2 gene and GC risk were systematically identified from PubMed databases. A meta-analysis was used to pool studies and to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of H. pylori babA2 gene associated with GC risk. Results Twenty studies were identified with a total of 1289 GC cases and 1081 controls. H. pylori babA2 gene was associated with an increased risk of GC by 2.05 fold (95% CI, 1.30–3.24, P = 0.002). In subgroup analysis, we found that H. pylori babA2 gene was significantly associated with GC risk in Asian population (OR = 2.63, 95% CI: 1.36–5.09 P = 0.004) but not in South American population (OR = 1.35, 95% CI: 0.69–2.64, P = 0.379). Conclusions This meta-analysis indicates that H. pylori babA2 gene may be associated with increased risk of GC, especially in Asian population.
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Affiliation(s)
- Marce-Amara Kpoghomou
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Jinchen Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Tianpei Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Guanfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. .,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China.
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Farzi N, Yadegar A, Aghdaei HA, Yamaoka Y, Zali MR. Genetic diversity and functional analysis of oipA gene in association with other virulence factors among Helicobacter pylori isolates from Iranian patients with different gastric diseases. INFECTION GENETICS AND EVOLUTION 2018; 60:26-34. [PMID: 29452293 DOI: 10.1016/j.meegid.2018.02.017] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 01/29/2018] [Accepted: 02/12/2018] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori (H. pylori) is one of the most genetically diverse bacterial pathogens that persistently colonizes the human gastric epithelium. This remarkable genomic plasticity may act as a driving force for successful adaptation and persistence of the bacteria in the harsh gastric environment. Outer inflammatory protein A (OipA) encoded by oipA gene (HP0638/hopH) is a member of the outer membrane proteins (OMPs) of H. pylori involved in induction of IL-8 secretion and is associated with development of peptic ulcer and gastric cancer. Expression of OipA is regulated by phase variation within a CT dinucleotide repeat motif of the oipA gene. In this study we carried out direct DNA sequence analysis of 53 amplified fragments to investigate the oipA "On/Off" status among Iranian H. pylori isolates from patients with various gastric diseases. The prevalence of cagL, cagA, EPIYA motifs, vacA alleles, babA2 and sabA genotypes as well as cagPAI integrity of the isolates were determined by PCR. Our results demonstrated a high prevalence of strains with functional oipA status (79%) and significant associations were found between functional oipA and cagA (P = 0.027) and vacA s1m1 (P = 0.022) genotypes. The vacA s1m2 genotype was also found to be statistically associated with PUD (P = 0.0001). Interestingly, we showed that H. pylori strains with intact cagPAI co-expressed oipA gene in a significant synergistic relationship (P < 0.01). However, no significant association was observed between the functional oipA status and clinical outcomes (P > 0.05). In conclusion, our findings denotes great diversity in the number and pattern of CT dinucleotide repeats of oipA among Iranian H. pylori strains. The synergistic link between functional oipA and other important virulence factors is proposed to be critical in the pathogenesis of H. pylori, which needs further studies with a larger number of samples.
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Affiliation(s)
- Nastaran Farzi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ying HY, Yu BW, Yang Z, Yang SS, Bo LH, Shan XY, Wang HJ, Zhu YJ, Wu XS. Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies. J Cell Mol Med 2016; 20:526-36. [PMID: 26805397 PMCID: PMC4759475 DOI: 10.1111/jcmm.12737] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 10/16/2015] [Indexed: 12/25/2022] Open
Abstract
Gastric cancer is one of the most common malignancies worldwide. Interleukin‐1‐beta (IL‐1β) is a pro‐inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL‐1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta‐analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta‐analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta‐regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL‐1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL‐1B 31T variant in the population‐based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03–1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL‐1B 31 polymorphism increased gastric cancer risk in infection‐positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02–1.78; heterozygous model: OR = 1.31, 95% CI = 1.04–1.66; recessive model: OR = 1.29, 95% CI = 1.04–1.61). The study suggested that IL‐1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene–environment interaction in gastric carcinogenesis.
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Affiliation(s)
- Hua-Yong Ying
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Bei-Wei Yu
- Department of Laboratory Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China
| | - Zong Yang
- The Fifth Medical Team, Xinjiang Uygur Autonomous Region Corps of Chinese People's Armed Police Forces, Xinjiang, China
| | - Shan-Shan Yang
- Department of Laboratory Medicine, Jinhua Woman & Children Health Hospital, Jinhua, Zhejiang, China
| | - Li-Hong Bo
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Xiao-Yun Shan
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Hui-Jiao Wang
- Department of Laboratory Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China
| | - Yi-Jun Zhu
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Xue-Song Wu
- School of Humanities and Social Science, Harbin Medical University, Harbin, Heilongjiang, China
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Wang Y, Wu H, Wu X, Bian Z, Gao Q. Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression. PLoS One 2014; 9:e96678. [PMID: 24905806 PMCID: PMC4048176 DOI: 10.1371/journal.pone.0096678] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 04/11/2014] [Indexed: 11/18/2022] Open
Abstract
Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in pathology of inflammatory diseases and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the invasiveness of gastric cancer (GC). In the study, we found that IL-17A could promote the migration and invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated, while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with helenalin, a nuclear factor-κB (NF-κB) inhibitor, was proved to abolish the promoting effect of IL-17A on the invasion ability of GC cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings illustrated that IL-17A could promote the invasion of GC cells by activating NF-κB pathway, and subsequently upregulating the expression of MMP-2 and MMP-9. These results may lead to the identification of new diagnostic markers and therapeutic targets of GC.
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Affiliation(s)
- Yidong Wang
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
| | - Hong Wu
- Department of General Surgery, XIAN XD GROUP Hospital, Xi’an, Shaanxi, P. R. China
| | - Xiaoling Wu
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
| | - Zhuoqiong Bian
- Department 5 of rheumatology, the fifth hospital of Xi’an city, Xi’an, Shaanxi, P. R. China
| | - Qing Gao
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
- * E-mail:
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Ozbey G, Demirel U, Aygun C, Ertas HB. Investigation of the association between clinical outcome and the cag pathogenicity-island and other virulence genes of Helicobacter pylori isolates from patients with dyspepsia in Eastern Turkey. Braz J Microbiol 2013; 44:1267-1274. [PMID: 24688521 PMCID: PMC3958197 DOI: 10.1590/s1517-83822013000400034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 04/04/2013] [Indexed: 12/15/2022] Open
Abstract
The aims of our work were to determine the presence of the cag pathogenicity-island (cag PAI) and other virulence genes of Helicobacter pylori recovered from patients with gastritis and peptic ulcer, and to investigate the correlation of these virulence genes with clinical outcome. The presence of the cagA, the promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA and oipA genes among 69 H. pylori isolates were determined by polymerase chain reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene was identified in 52.1% and 76.2% of isolates from patients with dyspepsia (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e. JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less than 25% of the isolates carried other ORFs. Types I, II and III were the most commonly found among the isolates. None of the isolates possessed type Ib, 1c, IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in isolates with peptic ulcer and gastritis, respectively. The results confirmed that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was significantly related to peptic ulcer (p < 0.05).
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Affiliation(s)
- Gokben Ozbey
- Vocational School of Health Services, Firat University, Elazig, Turkey
| | - Ulvi Demirel
- Department of Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Cem Aygun
- Department of Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Hasan Basri Ertas
- Department of Microbiology, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
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Ryberg A, Petersson F, Redeen S, Eriksson O, Borch K. Host Gene Polymorphisms in Relation to Helicobacter Pylori Infection and Associated Diseases in a Population Based Cohort. Gastroenterology Res 2013; 6:207-218. [PMID: 27785255 PMCID: PMC5051128 DOI: 10.4021/gr578w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2013] [Indexed: 12/12/2022] Open
Abstract
Background This prospective population based cohort study explores possible associations between host gene polymorphisms, blood group and life style factors on the one hand, and Helicobacter pylori infection, peptic ulcer, and the grade of inflammation, atrophy and intestinal metaplasia of the gastric mucosa, on the other hand. Methods The study population (472 volunteers) has previously undergone screening with gastroduodenoscopy, biopsy and blood sampling. The host gene polymorphisms of IL1B-31C/T, IFNGR1-56T/C, the IL1RN VNTR in exon 2 and the HLA-DRB1 gene alleles were analyzed using PCR and pyrosequencing. Results H. pylori infection was negatively related to HLA DRB1*03 (odds ratio (OR) 95% CI: 0.388 - 0.989) and was more frequent in individuals with blood group O than A (OR 95% CI: 1.121 - 2.677). There was a lower risk of moderate to severe inflammation in the antrum among individuals with IL1B-31 TC compared to CC carriers (OR 95% CI: 0.094 - 0.733). The IL1RN*L2 genotype was associated with higher risk of IM in the antrum than the *LL genotype (OR 95% CI: 1.570 - 15.878). There was a negative relation between the HLA DRB1 alleles *04 (OR 95% CI: 0.234 - 0.831) and *08 (OR 95% CI: 0.013 - 0.915), and IM in the antrum. Conclusion The IL1RN VNTR and the IL1β-31 alleles seem to be associated with intestinal metaplasia of the corpus mucosa and the grade of inflammation of the antrum, respectively. However, no unambiguous correlations could be identified between the host polymorphisms and the occurrence of H. pylori infection, peptic ulcer, and the grade of inflammation, atrophy and IM of the gastric mucosa.
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Affiliation(s)
- Anna Ryberg
- Department of Clinical Microbiology, Centre for Diagnostics, County Council of Ostergotland, Sweden; Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
| | - Fredrik Petersson
- Department of Pathology, National University Health System Singapore. Previously Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
| | - Stefan Redeen
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
| | - Olle Eriksson
- Department of Computer and Information Science, Faculty of Arts and Sciences, Linkoping University, Sweden
| | - Kurt Borch
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
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Zhang BB, Li Y, Feng JQ, Bian DL, Gao XM, Ran MY. No association between IL-1RN VNTR and the risk of duodenal ulcer: A meta-analysis. Hum Immunol 2013; 74:1170-8. [PMID: 23800434 DOI: 10.1016/j.humimm.2013.06.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2013] [Revised: 05/12/2013] [Accepted: 06/14/2013] [Indexed: 12/24/2022]
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Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development. Arch Immunol Ther Exp (Warsz) 2013; 61:503-12. [PMID: 23995914 PMCID: PMC3898137 DOI: 10.1007/s00005-013-0245-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Accepted: 08/05/2013] [Indexed: 12/20/2022]
Abstract
Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of –889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism –889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ2 = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04–2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.
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12
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Mattar R, Marques SB, Dos Santos AF, do Socorro Monteiro M, Iriya K, Carrilho FJ. A possible role of IL-1RN gene polymorphism in the outcome of gastrointestinal diseases associated with H. pylori infection. Clin Exp Gastroenterol 2013; 6:35-41. [PMID: 23637547 PMCID: PMC3634316 DOI: 10.2147/ceg.s42260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Objective To verify whether the variable number of tandem repeat (VNTR) polymorphism in the IL-1RN gene that encodes the interleukin (IL)-1 receptor antagonist (IL-1Ra) plays a role in the outcome of gastrointestinal diseases associated with Helicobacter pylori (H. pylori) infection. Methods Patients with normal endoscopy (n = 71), inflammation of the upper gastrointestinal tract only (n = 196), gastric ulcer (n = 28), duodenal ulcer (n = 76), and gastric cancer (n = 19) were studied. H. pylori infection was diagnosed by the urease test, histological examination, and polymerase chain reaction. The IL-1 receptor antagonist gene (IL-1RN intron 2 VNTR) was analyzed by polymerase chain reaction. Gastritis was scored according to the updated Sydney system of classification. Results H. pylori infection was an independent risk factor for mild (odds ratio [OR] = 5.53 [95% confidence interval [CI] = 2.63–11.64; P < 0.05]), moderate (OR = 83.93 [95% CI = 29.7–237.18; P < 0.05]) and marked (OR = 47.47 [95% CI = 5.39–418.05; P < 0.05]) gastritis. The carriage of IL-1RN*2/*2 had a significant protective effect of H. pylori infection (OR = 0.31 [95% CI = 0.17–0.57; P < 0.05]). H. pylori infection was identified as an independent risk of inflammation, duodenal ulcer, and gastric ulcer. The carriage of IL-1RN*2/*2 was an independent risk factor for gastric cancer (OR = 5.81 [95% CI = 1.06–31.98; P < 0.05]); nonetheless, the carriage of allele 2 (IL-1RN*2/*2 plus IL-1RN*L/*2) had an independent protective effect on duodenal ulcer (OR = 0.45 [95% CI = 0.22–0.91; P < 0.05]). Conclusions Allele 2 of the VNTR IL-1RN polymorphism had a protective effect against duodenal ulcer and H. pylori infection; however, it increased the risk of gastric cancer.
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Affiliation(s)
- Rejane Mattar
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, SP, Brazil
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Mitchell PJ, Afzali B, Fazekasova H, Chen D, Ali N, Powell N, Lord GM, Lechler RI, Lombardi G. Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1β production by dendritic cells. Clin Exp Immunol 2013; 170:300-9. [PMID: 23121671 DOI: 10.1111/j.1365-2249.2012.04659.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori is one of the most common infections in the world. Despite inciting inflammation, immunological clearance of the pathogen is often incomplete. CD4(+) CD25(hi) forkhead box protein 3 (FoxP3(+)) regulatory T cells (T(regs)) are potent suppressors of different types of immune responses and have been implicated in limiting inflammatory responses to H. pylori. Investigating the influence of H. pylori on T(reg) function and proliferation, we found that H. pylori-stimulated dendritic cells (DCs) induced proliferation in T(regs) and impaired their suppressive capability. This effect was mediated by interleukin (IL)-1β produced by H. pylori-stimulated DCs. These data correlated with in-vivo observations in which H. pylori(+) gastric mucosa contained more T(regs) in active cell division than uninfected stomachs. Inciting local proliferation of T(regs) and inhibiting their suppressive function may represent a mechanism for the chronic gastritis and carcinogenesis attributable to H. pylori.
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Affiliation(s)
- P J Mitchell
- MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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Zhang BB, Wang J, Bian DL, Chen XY. No association between IL-1β -31 C/T polymorphism and the risk of duodenal ulcer: a meta-analysis of 3793 subjects. Hum Immunol 2012; 73:1200-6. [PMID: 22917539 DOI: 10.1016/j.humimm.2012.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 07/24/2012] [Accepted: 08/09/2012] [Indexed: 12/11/2022]
Abstract
The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -31 C/T polymorphism and DU (allelic model: OR=0.96, 95%CI=0.86-1.07; additive model: OR=0.85, 95%CI=0.67-1.07; dominant model: OR=0.95, 95%CI=0.81-1.13; and recessive model: OR=0.95, 95%CI=0.79-1.15). Significant association was found in additive model for PB subgroup (OR=0.65, 95%CI=0.44-0.96) and recessive model for non-Asian subgroup (OR=0.72, 95%CI=0.52-0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β -31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.
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Affiliation(s)
- Bei-Bei Zhang
- Department of Medical Affairs, General Hospital of PLA Chengdu Military Area Command, Chengdu 610083, PR China.
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Zorzetto V, Maddalo G, Basso D, Farinati F. Immunotherapy for gastric premalignant lesions and cancer. Immunotherapy 2012; 4:587-99. [PMID: 22788127 DOI: 10.2217/imt.12.50] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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The Human Gastric Pathogen Helicobacter pylori and Its Association with Gastric Cancer and Ulcer Disease. ACTA ACUST UNITED AC 2011. [DOI: 10.1155/2011/340157] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
With the momentous discovery in the 1980's that a bacterium, Helicobacter pylori, can cause peptic ulcer disease and gastric cancer, antibiotic therapies and prophylactic measures have been successful, only in part, in reducing the global burden of these diseases. To date, ~700,000 deaths worldwide are still attributable annually to gastric cancer alone. Here, we review H. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and VacA), immune activation and the challenges posed by resistance to existing therapies. We consider also the important role of host-genetic variants, for example, in inflammatory response genes, in determining infection outcome and the role of H. pylori in other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions that H. pylori has protective effects in GERD and autoimmune diseases, such as asthma, have gained momentum. Therefore, we consider the basis for these suggestions and discuss the potential impact for future therapeutic rationales.
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Li J, Wang F, Zhou Q, Ou Z, Jia H, Deng X, He Y, Wu X. IL-1 polymorphisms in children with peptic symptoms in South China. Helicobacter 2011; 16:246-51. [PMID: 21585612 DOI: 10.1111/j.1523-5378.2011.00837.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Polymorphisms of IL-1 gene cluster are reported to be associated with histological changes and IL-1β expression in the gastric mucosa in adults, especially in Helicobacter pylori-infected subjects. As H. pylori infecting adults and children own different virulence genotypes, the aim of this study was to investigate whether IL-1 polymorphisms are risk factors in young children in South China. MATERIALS AND METHODS A total of 128 children with peptic symptoms were enrolled in this study. Polymorphisms of IL-1B-511 and IL-1B-31 were identified by dual fluorescence PCR. Variable number of tandem repeat region in IL-1RN was detected by conventional PCR and IL-1β mRNA expression by real-time PCR ddCT assay. RESULTS IL-1B-31T and IL-1B-511C were completely linked in this study. Significant differences of IL-1B-511/-31 genotypes were observed among different clinical outcomes (p = .001). The IL-1B-511TT/-31CC was mostly found in the moderate gastritis and the above (severe gastritis or gastric ulcer) groups, with percentage of 60.7%. While no association was observed between IL-1RN genotypes and the gastric mucosal histological changes (p = .128). Also no relationships were found between IL-1 polymorphisms and H. pylori infection or gastric mucosal IL-1β mRNA expression level. CONCLUSION Children with IL-1B-511TT/-31CC may have a risk to develop relatively severe gastric mucosal histological changes in South China.
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Affiliation(s)
- Juan Li
- Department of Laboratories, the Second Affiliated Hospital of GuangZhou Medical University, Guangzhou, China
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Persson C, Canedo P, Machado JC, El-Omar EM, Forman D. Polymorphisms in inflammatory response genes and their association with gastric cancer: A HuGE systematic review and meta-analyses. Am J Epidemiol 2011; 173:259-70. [PMID: 21178102 DOI: 10.1093/aje/kwq370] [Citation(s) in RCA: 138] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date.
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Affiliation(s)
- Christina Persson
- Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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Peleteiro B, Lunet N, Carrilho C, Durães C, Machado JC, La Vecchia C, Barros H. Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2010; 19:762-76. [PMID: 20200422 DOI: 10.1158/1055-9965.epi-09-0917] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Polymorphisms within interleukin-1 (IL1) and tumor necrosis factor alpha (TNFA) gene clusters are associated with an increased risk of gastric cancer. However, their role in gastric precancerous lesions remains poorly understood. Our objective was to perform a meta-analysis of studies addressing the association between IL1B-511, IL1RN variable number of tandem repeat, and TNFA-308 gene polymorphisms and gastric precancerous lesions, including original data from Portugal and Mozambique. Published studies on the association between these cytokine gene polymorphisms and gastric precancerous lesions were identified by systematic review, and estimates of the association were combined using random-effects meta-analysis taking into account new data obtained from Portuguese volunteer shipyard workers (n = 215) and Mozambican dyspeptic patients (n = 96) who underwent endoscopic and pathologic evaluation following the same protocol. Odds ratio (OR) estimates for intestinal metaplasia were 2.83 [95% confidence interval (95% CI), 1.15-6.96] for the IL1RN*22 genotype, 1.86 (95% CI, 1.03-3.36) for IL1B-511 T carriers, and 0.59 (95% CI, 0.12-3.04) for the TNFA-308*AA genotype in the Portuguese sample. All Mozambican subjects with intestinal metaplasia were T carriers for IL1B-511 and none had the 2 allele for IL1RN. In meta-analysis, IL1RN*22 genotype was associated with an increased risk of gastric precancerous lesions (22 versus LL: OR, 2.27; 95% CI, 1.40-3.70; I(2) = 26.4%; 12 studies). No such association was found for the IL1B-511 (TT versus CC: OR, 1.34; 95% CI, 0.87-2.07; I(2) = 65.7%; 13 studies) or TNFA-308 genotypes (AA versus GG: OR, 0.93; 95% CI, 0.35-2.43; I(2) = 0.0%; 7 studies). The IL1RN*22 genotype seems to consistently increase the risk of gastric precancerous lesions, supporting a role for this polymorphism in the early stages of gastric carcinogenesis.
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Affiliation(s)
- Bárbara Peleteiro
- Serviço de Higiene e Epidemiologia, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
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Con SA, Takeuchi H, Con-Chin GR, Con-Chin VG, Yasuda N, Con-Wong R. Role of bacterial and genetic factors in gastric cancer in Costa Rica. World J Gastroenterol 2009; 15:211-8. [PMID: 19132772 PMCID: PMC2653314 DOI: 10.3748/wjg.15.211] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR).
METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1&bgr; and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes.
RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1&bgr;+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4).
CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.
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Gutiérrez-González L, Wright NA. Biology of intestinal metaplasia in 2008: more than a simple phenotypic alteration. Dig Liver Dis 2008; 40:510-22. [PMID: 18400571 DOI: 10.1016/j.dld.2008.02.029] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2008] [Accepted: 02/18/2008] [Indexed: 12/11/2022]
Abstract
This review concentrates on one main aspect of cancerization in the oesophagus and stomach: principally, intestinal metaplasia. There are at least two other important pathways that lead to cancer and do not need such a morphological transformation. One is the gastric type of carcinoma on the Lauren classification, which arises directly from the stem cell zone and is the signet ring form of cancer, while the other is spasmolytic polypeptide-expressing metaplasia (SPEM)--spasmolytic polypeptide (TFF2) expressing metaplasia, where the gastric glands become filled with TFF2-expressing cells and may also lead to gastric dysplasia and cancer. The development of intestinal metaplasia is complex. Here, we examine intestinal metaplasia in molecular terms, noting the over-expression of Cdx1, Cdx2, Pdx1, Oct1, TFF3 and the downregulation of Hedgehog signalling; Runx3 is deactivated by epigenetic silencing, and pathways such as Wnt and MARK/ERK are involved. These changes start to explain the principles of the development of intestinal metaplasia and suggest that the regulation of these genes is of importance in the development of gastric cancer.
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Saxena A, Prasad KN, Ghoshal UC, Bhagat MR, Krishnani N, Husain N. Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection: A study from northern India. World J Gastroenterol 2008; 14:1498-503. [PMID: 18330937 PMCID: PMC2693741 DOI: 10.3748/wjg.14.1498] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non-ulcer dyspepsia (NUD).
METHODS: We enrolled 348 adult patients (62 gastric adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests (RUT, culture, histopathology and PCR) were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by PCR-RFLP analysis.
RESULTS: Frequency of C carrier had significant association with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs 31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09-19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients with C carrier and H pylori infection had significant risk for the development of PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34).
CONCLUSION: -765G > C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.
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IL-4 -588C>T polymorphism and IL-4 receptor alpha [Ex5+14A>G; Ex11+828A>G] haplotype concur in selecting H. pylori cagA subtype infections. Clin Chim Acta 2007; 389:139-45. [PMID: 18179773 DOI: 10.1016/j.cca.2007.12.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2007] [Revised: 12/07/2007] [Accepted: 12/07/2007] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Th2 cytokine IL-4 might limit H. pylori associated gastric inflammation and favour H. pylori clearance. The aim of the study was to verify whether IL-4 -588C>T SNP, or two SNPs of the gene coding the alpha chain of IL-4 receptor (IL-4RA Ex5+14A>G, IL-4RA Ex11+828A>G) considered singly or as haplotypes, are correlated with H. pylori virulence genes or H. pylori associated diseases. METHODS We studied 144 patients with non-cardia gastric cancer (NCGC)(41/50 with present or past H. pylori infection), 75 with duodenal ulcer (DU)(66 H. pylori infected) and 171 with gastritis (CG)(107 H. pylori infected). cagA gene was present in 24/28 NCGC, 45/59 DU and 56/107 CG. RESULTS All SNPs were in Hardy-Weinberg equilibrium. IL-4RA haplotypes frequencies were estimated using Arlequin software. Neither the SNPs nor the IL-4RA haplotype correlated with disease diagnosis, H. pylori infection, degree of mucosal inflammation or intestinal metaplasia. IL-4 -588T allele (OR=3.69, 95% CI:1.34-10.16) and IL-4RA GA haplotype (p<0.05) enhanced the risk for cagA positive infections. IL-4RA GA haplotype correlated with IL-4 protein levels in H. pylori infected gastric mucosa. CONCLUSIONS IL-4 and IL-4RA gene polymorphisms concur in selecting the H. pylori infecting strain, probably influencing the IL-4 signalling pathway.
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Zambon CF, Fasolo M, Basso D, D'Odorico A, Stranges A, Navaglia F, Fogar P, Greco E, Schiavon S, Padoan A, Fadi E, Sturniolo GC, Plebani M, Pedrazzoli S. Clarithromycin resistance, tumor necrosis factor alpha gene polymorphism and mucosal inflammation affect H. pylori eradication success. J Gastrointest Surg 2007; 11:1506-14; discussion 1514. [PMID: 17846855 DOI: 10.1007/s11605-007-0246-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2007] [Accepted: 07/12/2007] [Indexed: 01/31/2023]
Abstract
Several bacterial and host-related factors concur in causing Helicobacter pylori eradication failure. We ascertained the role of bacterial virulence genes (cagA, vacA), clarithromycin resistance [Cla(R), 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-gamma+874A>T, TNF-alpha-1031T>C, TNF-alpha-857C>T, TNF-alpha-376G>A, TNF-alpha-308G>A, TNF-alpha-238G>A, IL-10-1082A>G, IL-10-819C>T, IL-10-592C>A, IL-12A+6686G>A, IL-12B+15485A>C. Two groups of H. pylori-infected and H. pylori-treated patients were retrospectively identified: 45 not eradicated and 57 eradicated. Treatment failure was significantly correlated with Cla(R) (all resistant strains in non-eradicated patients); with TNF-alpha-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering Cla(S)-infected patients only, logistic regression analysis (eradication = dependent; TNF-alpha-238, IL12B + 15485 genotypes, IL10 ATA/ATA as present or absent, antral gastritis grade = covariates) confirmed as significantly correlated with eradication antral gastritis grade only (Exp(B) = 6.48; 95% CI, 1.2-35.01). In conclusion, the bacterial determinant causing triple therapy failure is clarithromycin resistant, being virulence genes not involved. The host related factors that favor eradication are those linked to inflammation: a higher inflammatory infiltrate in the mucosa, possibly favored by genotypes able to down regulate the anti-inflammatory cytokine response, enhance the chance of eradication success.
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Zhou Y, Toh ML, Zrioual S, Miossec P. IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. Cytokine 2007; 38:157-64. [PMID: 17644350 DOI: 10.1016/j.cyto.2007.06.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2007] [Revised: 05/24/2007] [Accepted: 06/04/2007] [Indexed: 01/22/2023]
Abstract
Inflammatory processes are implicated in gastric cancer development. In contrast, the role of inflammation and proinflammatory cytokines in established cancer remains to be clarified. We investigated the contribution of IL-17A versus IL-17F-mediated intracellular signalling pathways in human gastric adenocarcinoma AGS cells. IL-8 secretion was evaluated by ELISA, mitogen-activated protein kinase (MAPK)(4) by Western blotting, and activator protein 1(AP-1) and nuclear factor kappa B (NFkappaB) by TransAM transcription factor assay or qRT-PCR. IL-17RA and IL-17RC inhibition were achieved by small interfering RNA (siRNA). IL-17A significantly induced activation of all three MAPK (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NFkappaB. IL-17F was less potent but induced a significant activation of p65 NFkappaB. Consistently, IL-17A was more potent to induce IL-8 secretion than IL-17F. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-17A-mediated c-Jun and p65 activation. These data suggest that in gastric cancer, absence of either IL-17RA or IL-17RC can inhibit IL-17 responsiveness. Conversely, downstream of IL-17R binding, IL-17A and IL-17F induce key signal transduction pathways implicated in inflammation and carcinogenesis. IL-17A, and possibly IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer.
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MESH Headings
- Base Sequence
- Cell Line, Tumor
- DNA Primers/genetics
- DNA, Neoplasm/genetics
- DNA, Neoplasm/metabolism
- Genes, fos/drug effects
- Genes, jun/drug effects
- Humans
- Interleukin-17/metabolism
- Interleukin-17/pharmacology
- Interleukin-8/biosynthesis
- MAP Kinase Signaling System/drug effects
- NF-kappa B/metabolism
- RNA Interference
- RNA, Small Interfering/genetics
- Receptors, Interleukin/antagonists & inhibitors
- Receptors, Interleukin/genetics
- Receptors, Interleukin-17/antagonists & inhibitors
- Receptors, Interleukin-17/genetics
- Recombinant Proteins/pharmacology
- Signal Transduction/drug effects
- Stomach Neoplasms/genetics
- Stomach Neoplasms/immunology
- Stomach Neoplasms/metabolism
- Transcription Factor AP-1/metabolism
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Affiliation(s)
- Yuan Zhou
- Department of Immunology & Rheumatology, Mixed Unit Hospices Civils de Lyon-BioMérieux, E. Herriot Hospital, 69437 Lyon Cedex 03, France
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Kamangar F, Cheng C, Abnet CC, Rabkin CS. Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis. Cancer Epidemiol Biomarkers Prev 2007; 15:1920-8. [PMID: 17035400 DOI: 10.1158/1055-9965.epi-06-0267] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Some studies have reported that proinflammatory polymorphisms in interleukin-1B (IL-1B) and IL-1 receptor antagonist (IL-1RN) genes are associated with increased gastric cancer risk. However, other studies have shown null or inverse associations. This meta-analysis reviews and summarizes published evidence for these associations. Searching the PubMed Database yielded 35 studies that reported on the association between IL-1B -511 C>T, IL-1B -31 T>C, or IL-1RN variable number tandem repeat polymorphisms and gastric cancer risk. Q-statistics and I(2) statistics were calculated to examine heterogeneity. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the random-effects model using the DerSimonian-Laird method. For all gastric cancers, the overall ORs (95% CIs) for IL-1B -511 CT versus CC and TT versus CC genotypes were 1.07 (0.91-1.25) and 1.16 (0.95-1.42), respectively. ORs (95% CIs) for the association between IL-1B -31 CT versus TT and CC versus TT genotypes were 0.99 (0.83-1.19) and 0.98 (0.78-1.21), respectively. For the associations between IL-1RN and gastric cancer, ORs (95% CIs) for *2/L versus LL and *2/*2 versus L/L were 1.15 (0.96-1.38) and 1.23 (0.79-1.92). For each of the examined associations, there was significant heterogeneity among studies; P(heterogeneity) < or = 0.001 and I(2) ranged from 0.54 to 0.71. Noncardia cancers showed stronger associations with IL-1B -511 CT or TT and IL1-RN *2/*2 genotypes, but limiting the analysis to intestinal-type cancers, studies conducted in Western countries, or studies in which polymorphisms were in Hardy-Weinberg equilibrium, made no material difference in the results. The overall associations between IL-1B or IL-1RN proinflammatory polymorphisms and gastric cancer were null but several studies showed an association. The sources of this variation are unclear.
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Affiliation(s)
- Farin Kamangar
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, Room 3034, Bethesda, MD 20892-7232, USA.
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Abstract
Isolation of the gastric spiral bacterium Helicobacter pylori totally reversed the false dogma that the stomach was sterile. In addition to its causal role in peptic ulceration, the newly identified bacterium has now been implicated in other gastric and even extragastric diseases, including chronic atrophic gastritis, gastric MALT lymphoma, gastric cancer, functional dyspepsia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, chronic urticaria, ischemic heart disease, and others. The majority of the reports are anecdotal, epidemiologic, or eradication studies, but there are also relevant in vitro studies. ITP represents one disease showing a strong link with H pylori infection. There are also accumulating data on the role of H pylori infection in iron deficiency anemia and ischemic heart disease. In summary, the association between H pylori infection and other extragut diseases is still controversial but worthy of further investigation.
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Affiliation(s)
- Hidekazu Suzuki
- Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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28
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Yilmaz O, Dursun H, Gürsan N, Pirim I, Yilmaz A, Okcu N. Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy in H pylori infected or noninfected gastroduodenal disease. World J Gastroenterol 2007; 13:1243-6. [PMID: 17451207 PMCID: PMC4147001 DOI: 10.3748/wjg.v13.i8.1243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between myelo-peroxidase polymorphisms as a host-related factor and atrophy caused by H pylori.
METHODS: Our study enrolled 77 patients. Biopsy materials obtained during gastrointestinal endoscopies were evaluated for the presence of H pylori. Polymerase chain reaction-restriction fragment length polymorphism assay was used to characterize myeloperoxidase genotypes.
RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1 (1.29%) had AA genotype. The change in atrophy in relation to neutrophil infiltration was significant in Hp (+) patients (P = 0.0001). The change in atrophy in relation to neutrophil infiltration in patients with GG genotype was significant (P = 0.002). However, the change in atrophy in relation to neutrophil infiltration was not significiant in patients with Hp (+) GG genotype (r = 0.066, P = 0.63).
CONCLUSION: Myeloperoxidase genotype is critical for development of atrophy in relation to the severity of inflammation. However, it is interesting to note that, H pylori does not show any additive effect on development of atrophy.
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Affiliation(s)
- Omer Yilmaz
- Department of Gastroenterology, University of Atatürk, Erzurum 25070, Turkey.
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29
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Wang P, Xia HHX, Zhang JY, Dai LP, Xu XQ, Wang KJ. Association of interleukin-1 gene polymorphisms with gastric cancer: a meta-analysis. Int J Cancer 2007; 120:552-562. [PMID: 17096351 DOI: 10.1002/ijc.22353] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, -31C, +3954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.
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Affiliation(s)
- Ping Wang
- School of Public Health, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
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30
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Li K, Tang ZP, Zheng FJ, Hong YS. Discussion on the reversibility of gastric intestinal metaplasia. Shijie Huaren Xiaohua Zazhi 2007; 15:140-144. [DOI: 10.11569/wcjd.v15.i2.140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric intestinal metaplasia (IM), as precancerous lesion of the stomach, is closely associated with the development of gastric cancer. Whether gastric IM can be reversed is still in controversy. Epidemiological evidence showed that IM was reversible after long-term following up, but the reversed degree was low. Besides H pylori infection, deficiency of vitamin C in the gastric mucosa, shortage of gastric acid and/or bile reflux can cause this precancerous condition. The pathogenesis of gastric IM, in which H pylori virulence factors, intestine-specific transcription factors, and microsatellite instability are involved, is being investigated at the present time, but it can't be affirmed that IM is a kind of phenotype alteration in gastric epithelial cells induced by stem cell mutation. It is fairly difficult to make diagnosis for IM unless careful endoscopic evaluation is performed and proper biopsy sites are selected. Eradication of H pylori alone may not be enough to reverse IM, and its combination with other chemopreventive agents and/or Chinese medicine may be an effective strategy.
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31
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Abstract
Mannose-binding lectin (MBL) is a pattern-recognition molecule that binds to characteristic carbohydrate motifs present on the surface of many different pathogens. MBL binding stimulates the immune system via the lectin pathway of complement activation. In certain clinical situations, often characterized by pre-existing immune compromise, MBL deficiency increases the risk of infectious and other disease-specific complications. Many of the key pathogenic processes inherent to common gastroenterological diseases, such as infection, immunological damage, and carcinogenesis, have been linked to MBL. This editorial reviews the biology of MBL, outlines key disease associations to document the breadth of influence of MBL, and finally, highlights the relevance of MBL to both gastroenterological health and disease.
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Affiliation(s)
- Daniel-L Worthley
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Room 3D230, Bedford Park, SA, 5042, Australia.
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32
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 and 1=1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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33
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 and 1>1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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34
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 or (1,2)=(select*from(select name_const(char(111,108,111,108,111,115,104,101,114),1),name_const(char(111,108,111,108,111,115,104,101,114),1))a) -- and 1=1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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35
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Abstract
Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.
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Affiliation(s)
- Johannes G Kusters
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
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36
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Greco E, Basso D, Fogar P, Mazza S, Navaglia F, Zambon CF, Falda A, Pedrazzoli S, Ancona E, Plebani M. Pancreatic cancer cells invasiveness is mainly affected by interleukin-1beta not by transforming growth factor-beta1. Int J Biol Markers 2006; 20:235-41. [PMID: 16398405 DOI: 10.1177/172460080502000406] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND We investigated in vitro whether IL-1beta and TGF-beta1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. MATERIALS AND METHODS Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1beta and TGF-beta1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. RESULTS Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1beta did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-beta1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. CONCLUSIONS IL-1beta enhances the invasive capacity of pancreatic cancer cells, whereas TGF-beta1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-beta1 signaling in pancreatic cancer treatment.
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Affiliation(s)
- E Greco
- Department of Laboratory Medicine, University Hospital of Padua, Italy
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37
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Kornman KS. Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr 2006; 83:475S-483S. [PMID: 16470016 DOI: 10.1093/ajcn/83.2.475s] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Inflammation plays a central role in many diseases of aging, and genetic differences in the inflammatory response appear to influence different disease courses among individuals. Variations in the genes for the family of interleukin 1 (IL-1) proteins are inherited together in a small set of patterns and provide an example of the role of inflammatory genetics as a modifier of diseases of aging. The IL-1 genetic variations are associated with variation in both the inflammatory response and the clinical presentation of a range of diseases, including coronary artery disease, Alzheimer disease, gastric cancer, and periodontitis. This growing understanding of the role of genetic variation in inflammation and chronic disease presents opportunities to identify healthy persons who are at increased risk of disease and to potentially modify the trajectory of disease to prolong healthy aging. Nutrition represents one of the promising approaches to modulation of the risk of diseases of aging because of the effects of certain nutrients on gene expression. One of the most practical applications of nutritional modulation of chronic disease may be nutrients that regulate the expression of key inflammatory genes.
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38
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Ando T, Goto Y, Maeda O, Watanabe O, Ishiguro K, Goto H. Causal role of Helicobacter pylori infection in gastric cancer. World J Gastroenterol 2006; 12:181-6. [PMID: 16482615 PMCID: PMC4066024 DOI: 10.3748/wjg.v12.i2.181] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori (H pylori) is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of H pylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.
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39
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Zabaleta J, Camargo MC, Piazuelo MB, Fontham E, Schneider BG, Sicinschi LA, Ferrante W, Balart L, Correa P, Ochoa AC. Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians. Am J Gastroenterol 2006; 101:163-71. [PMID: 16405550 DOI: 10.1111/j.1572-0241.2006.00387.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Interleukin-1beta plays an important role in inflammation and gastric physiology. Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects. The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians. METHODS Genomic DNA was extracted from gastric biopsies of 269 adult outpatients (172 African Americans and 97 Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological diagnosis was evaluated according to the updated Sydney System and H. pylori status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (-511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR-RFLP. Logistic regression models were used to identify variables associated with multifocal atrophic gastritis in terms of odds ratios and 95% confidence intervals. RESULTS Considering subjects with normal histology and nonatrophic gastritis as controls, a significant association was found between IL1B+3954T carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses stratified by ethnic group demonstrated similar associations in both African Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74, 5.65). A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis. The remaining proinflammatory polymorphisms were not associated with this precancerous lesion. CONCLUSIONS Our results suggest that the presence of IL1B+3954T allele is a risk marker for multifocal atrophic gastritis in the population studied.
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Affiliation(s)
- Jovanny Zabaleta
- Department of Pathology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
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40
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Abstract
Over the past 20 years, there has been marked progress in our understanding of the role of genetic and environmental factors in the etiology of gastroduodenal disease. Helicobacter pylori infection now is recognized to be the most important environmental factor for both noncardia gastric cancer and peptic ulcer disease. The likelihood of the infection resulting in significant disease depends on genetic polymorphisms influencing the virulence of the organism. However, the specific pattern of disease induced by the infection is determined to a great extent by genetic polymorphisms in the host that govern the local gastric immune response elicited. Genetic factors also are important in the treatment of gastroduodenal diseases. Polymorphisms of host CYP2C19 influence the pharmacokinetics and clinical efficacy of proton pump inhibitor therapy.
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Affiliation(s)
- Derek Gillen
- Division of Gastroenterology, Department of Medicine and Therapeutics, The University of Glasgow, The Western Infirmary, Glasgow, Scotland, United Kingdom.
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41
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Ouburg S, Bart A Crusius J, Klinkenberg-Knol EC, Mulder CJJ, Salvador Peña A, Morré SA. A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections. Eur J Gastroenterol Hepatol 2005; 17:1213-24. [PMID: 16215434 DOI: 10.1097/00042737-200511000-00010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.
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Affiliation(s)
- Sander Ouburg
- Department of Gastroenterology, Laboratory of Immunogenetics VU University Medical Centre, Amsterdam, The Netherlands
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42
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Queiroz DMM, Bittencourt P, Guerra JB, Rocha AMC, Rocha GA, Carvalho AST. IL1RN polymorphism and cagA-positive Helicobacter pylori strains increase the risk of duodenal ulcer in children. Pediatr Res 2005; 58:892-6. [PMID: 16183821 DOI: 10.1203/01.pdr.0000181380.14230.8b] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Duodenal ulcers in children are associated with Helicobacter pylori gastric infection with cagA-positive strains, but factors linked to the host are poorly known. The authors evaluated the role of proinflammatory interleukin-1 gene cluster polymorphisms in the pathogenesis of duodenal ulcer. They studied prospectively 437 children 1 to years old, 209 of whom were H. pylori positive and 228 of whom were H. pylori negative. IL1B-511-C/T, -31T/C, and IL1RN Variable number of tandem repeats were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism, PCR with confronting two-pair primers, and PCR, respectively. cagA status was evaluated by PCR. The role of the proinflammatory cytokine genotypes in the genesis of duodenal ulcer was evaluated before and after stratification of H. pylori status on logistic regression models. In the group of children without duodenal ulcer, no association was observed between H. pylori status and proinflammatory polymorphisms. Furthermore, no association between IL1 cluster genotypes and cagA status was seen in the H. pylori-positive children. However, increasing age, male sex, and IL1RN*2 were independently associated with duodenal ulcer. After stratification, in the H. pylori-positive children, increasing age, male sex, the presence of ILRN*2 allele, and cagA-positive status were independently associated with duodenal ulcer. The risk for the development of duodenal ulcer increased when a combined association of the presence of IL1RN*2 allele and infection by a cagA-positive H. pylori strain was the variable. This study provides evidence supporting independent roles of IL1RN*2 allele and cagA-positive status in the genesis of duodenal ulcer in children.
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Palli D, Saieva C, Luzzi I, Masala G, Topa S, Sera F, Gemma S, Zanna I, D'Errico M, Zini E, Guidotti S, Valeri A, Fabbrucci P, Moretti R, Testai E, del Giudice G, Ottini L, Matullo G, Dogliotti E, Gomez-Miguel MJ. Interleukin-1 gene polymorphisms and gastric cancer risk in a high-risk Italian population. Am J Gastroenterol 2005; 100:1941-8. [PMID: 16128937 DOI: 10.1111/j.1572-0241.2005.50084.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Host genetic factors, including the IL1 gene cluster, play a key role in determining the long-term outcome of Helicobacter pylori infection. The aim of the study was to investigate the relationship between selected IL1 loci polymorphisms and gastric cancer risk in an Italian population. METHODS In a case-control study we compared the IL1B-31 and IL1B+3954 biallelic and IL1RN pentaallelic variable number of tandem repeats (VNTR) polymorphisms in 185 gastric cancer patients and 546 controls randomly sampled from the general population of an area at high gastric cancer risk (Tuscany, Central Italy). RESULTS Genotype frequencies of the IL1B-31 T/C, IL1B+3954 C/T, and IL1RN polymorphisms among our population controls were in Hardy-Weinberg equilibrium. In multivariate analyses, no increase in gastric cancer risk was observed for the IL1B-31*C- and IL1B+3954*T- carriers; a significant 50% increase emerged for IL1RN*2 allele carriers (OR = 1.49; 95% CI: 1.01-2.21). Analyses based on combined genotypes showed also that the association with IL1RN*2 allele was limited to two-variant allele carriers who were also homozygous for the IL1B-31*T allele (OR = 2.23; 95% CI: 1.18-4.23) with a statistically significant interaction between these two genotypes (p= 0.043). Haplotype analysis showed an increased risk for the haplotype IL1RN*2/IL1B-31*T. CONCLUSIONS Our results suggest that host genetic factors (such as the IL1RN and the IL1B-31 polymorphisms) interact in the complex process of gastric carcinogenesis in this high-risk Italian population. Overall, this effect appears more modest than previously reported in other populations, supporting the hypothesis that other still-to-be-defined factors are important in gastric carcinogenesis. These findings might be due to a haplotype effect.
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Affiliation(s)
- D Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center (CSPO), Scientific Institute of Tuscany, Florence, Italy
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Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Gastric mucosal cytokine levels in relation to host interleukin-1 polymorphisms and Helicobacter pyloricagA genotype. Scand J Gastroenterol 2005; 40:530-9. [PMID: 16036505 DOI: 10.1080/00365520510012299] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The outcome of a Helicobacter pylori infection is related in part to interrelationships among H. pylori virulence factors and the H. pylori-induced mucosal response. The host inflammatory response is partly governed by polymorphisms in pro-inflammatory genes. MATERIAL AND METHODS Cytokine levels (interleukin (IL)-1beta, IL-6 and IL-8) were examined in H. pylori-infected and uninfected normal-appearing mucosa from patients with non-ulcer dyspepsia (NUD), margins of gastric ulcers and cancer tissues. Cytokine levels were compared with cagA genotypes and host interleukin (IL)-1 polymorphisms. RESULTS The study comprised 168 Thai patients. All infected patients possessed anti-CagA antibody. Gastric mucosal IL-8 levels were significantly higher in H.pylori-positive cases than in -negative cases in all three tissue types (e.g. 1115 versus 217 pg/mg protein for NUD) (p<0.001). Normal-appearing but H. pylori-infected antral mucosa of patients with cagA type 1a strains had higher IL-8 levels than those with type 2a strains (2632 versus 1036 pg/mg protein) (p<0.005). IL-1B-511T/T carriers had higher antral mucosal IL-1ss levels versus non-carriers (pg/mg protein) (T/T=221, T/C=178, C/C=70) (p=0.005). IL-1B-511T/T carriers also had higher IL-1beta levels versus non-carriers in H. pylori-negative patients. CONCLUSIONS It was found that both the host factors (IL-1 polymorphisms) and bacterial factors (cagA type 1a versus type 2a) influenced gastric mucosal cytokine levels. Future studies should concentrate on interactions among host factors (e.g. genetics and tissue responses) and bacterial and environmental factors.
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Perri F, Piepoli A, Bonvicini C, Gentile A, Quitadamo M, Di Candia M, Cotugno R, Cattaneo F, Zagari MR, Ricciardiello L, Gennarelli M, Bazzoli F, Ranzani GN, Andriulli A. Cytokine gene polymorphisms in gastric cancer patients from two Italian areas at high and low cancer prevalence. Cytokine 2005; 30:293-302. [PMID: 15927855 DOI: 10.1016/j.cyto.2005.01.011] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2004] [Revised: 01/12/2005] [Accepted: 01/25/2005] [Indexed: 12/15/2022]
Abstract
Polymorphisms of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL1-RN), and tumor necrosis factor-alpha (TNF-alpha) genes are supposed to be key determinants of gastric cancer risk. Our aim was to study the association between these polymorphisms and gastric cancer in two areas characterized by high (Pavia/Bologna, North Italy) and low (San Giovanni Rotondo, South Italy) gastric cancer prevalence. Genomic DNA was obtained from 216 healthy donors and 98 gastric cancer patients from Pavia and Bologna, and 146 healthy donors and 86 gastric cancer patients from San Giovanni Rotondo. Two SNP in IL-1beta (-511 C/T) and TNF-alpha (-308 G/A) as well as the VNTR polymorphism of IL-1RN locus were studied. A significant linkage disequilibrium was found between IL-1beta -511 and IL-1RN. Genotype and allele frequencies at the IL-1beta, IL-1RN, and TNF-alpha loci in gastric cancer cases were not significantly different from controls. An epistatic effect between IL-1beta -511 and IL-1RN was found with the IL-1beta -511C/IL-1RN*2 haplotype conferring a significant protection against the intestinal-type of gastric cancer in the Southern population. In conclusion, IL-1beta, IL1-RN, and TNF-alpha genotypes are not associated with gastric cancer in Italian patients. An epistatic interrelationship between IL-1beta -511 and IL-1RN confers protection against gastric cancer in low-risk Italian population.
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Affiliation(s)
- F Perri
- Department and Research Laboratory of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, 71013 San Giovanni Rotondo, Italy.
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Pillinger MH, Marjanovic N, Kim SY, Scher JU, Izmirly P, Tolani S, Dinsell V, Lee YC, Blaser MJ, Abramson SB. Matrix metalloproteinase secretion by gastric epithelial cells is regulated by E prostaglandins and MAPKs. J Biol Chem 2005; 280:9973-9. [PMID: 15640153 DOI: 10.1074/jbc.m413522200] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Because matrix metalloproteinases (MMPs) play roles in inflammatory tissue injury, we asked whether MMP secretion by gastric epithelial cells may contribute to gastric injury in response to signals involved in Helicobacter pylori-induced inflammation and/or cyclooxygenase inhibition. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and epidermal growth factor (EGF) stimulated gastric cell MMP-1 secretion, indicating that MMP-1 secretion occurs in inflammatory as well as non-inflammatory situations. MMP-1 secretion required activation of the MAPK Erk and subsequent protein synthesis but was down-regulated by the alternate MAPK, p38. In contrast, secretion of MMP-13 was stimulated by TNF-alpha/IL-1beta but not EGF and was Erk-independent and mediated by p38. MMP-13 secretion was more rapid (peak, 6 h) than MMP-1 (peak > or =30 h) and only partly depended on protein synthesis, suggesting initial release of a pre-existing MMP-13 pool. Therefore, MMP-1 and MMP-13 secretion are differentially regulated by MAPKs. MMP-1 secretion was regulated by E prostaglandins (PGEs) in an Erk-dependent manner. PGEs enhanced Erk activation and MMP-1 secretion in response to EGF but inhibited Erk and MMP-1 when TNF-alpha and IL-1beta were the stimuli, indicating that the effects of PGEs on gastric cell responses are context-dependent. These data show that secretion of MMPs is differentially regulated by MAPKs and suggest mechanisms through which H. pylori infection and/or cyclooxygenase inhibition may induce epithelial cell signaling to contribute to gastric ulcerogenesis.
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Affiliation(s)
- Michael H Pillinger
- Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
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Rolle-Kampczyk UE, Fritz GJ, Diez U, Lehmann I, Richter M, Herbarth O. Well water--one source of Helicobacter pylori colonization. Int J Hyg Environ Health 2004; 207:363-8. [PMID: 15471100 DOI: 10.1078/1438-4639-00301] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Helicobacter pylori (H. pylori) is one of the world's most widespread microorganisms. Its acquisition in humans remains poorly understood, however, epidemiological studies have identified drinking water as reservoir for the bacterium. The aim of this study was to investigate the prevalence of H. pylori infection among individuals using or drinking previously H. pylori tested well water. Applying household cluster sampling, a total of 91 subjects, all using or drinking well water (13 of either H. pylori positive or negative wells), were screened for their H. pylori status. The group was comprised of 73 adults and 19 children under the age of 18. H. pylori infection was determined using the [13C]urea breath test. A self-administered or parent-completed questionnaire provided information on living conditions and lifestyle habits including the use or drinking of well water. Logistic regression analyses associated the drinking of H. pylori positive well water with a positive colonization status [Odds Ratio (OR) 8.3; 95% confidence interval (95% CI) 2.4-29]. In summary, the use or drinking of H. pylori contaminated well water appears associated with the acquisition of a H. pylori infection. This study is based on a relatively small and inhomogeneous population sample and should be repeated to confirm the results.
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Affiliation(s)
- Ulrike E Rolle-Kampczyk
- Centre for Environmental Research Leipzig-Halle, Department of Human Exposure Research and Epidemiology, Leipzig, Germany.
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Hsu PI, Li CN, Tseng HH, Lai KH, Hsu PN, Lo GH, Lo CC, Yeh JJ, Ger LP, Hsiao M, Yamaoka Y, Hwang IR, Chen A. The interleukin-1 RN polymorphism and Helicobacter pylori infection in the development of duodenal ulcer. Helicobacter 2004; 9:605-613. [PMID: 15610073 DOI: 10.1111/j.1083-4389.2004.00277.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The host genetic factors that determine the clinical outcomes for Helicobacter pylori-infected individuals remain unclear. AIMS To elucidate the relations among interleukin-1 locus polymorphisms, and H. pylori infection in the development of duodenal ulcers. MATERIALS AND METHODS In a case-control study involving 168 control subjects and 147 patients with duodenal ulcer, biallelic polymorphisms of two interleukin-1 loci, IL-1B(-511) and IL-1B(+3954), as well as the penta-allelic variable number of tandem repeats of interleukin-1 receptor antagonist IL-1RN, were genotyped, and the H. pylori states of controls and patients were examined. RESULTS Helicobacter pylori infection, male gender and the carriage of IL-1RN*2 independently increased the risk of duodenal ulcer with odds ratios of 6.4 (95% confidence interval, 3.7-11.0), 1.9 (95% confidence interval, 1.1-3.4) and 2.7 (95% confidence interval, 1.1-6.8), respectively. Statistical analysis revealed an interaction between IL-1RN*2 and H. pylori infection with the duodenal ulcer risk conferred by the H. pylori infection substantially increased (odds ratios, 22.6; 95% confidence interval, 5.9-86.5) by the carriage of IL-1RN*2. In addition, a synergistic interaction between IL-1RN*2 and blood group O existed. The combined risk of H. pylori infection, the carriage of IL-1RN*2 and blood group O for duodenal ulcer was 27.5 (95% confidence interval, 3.1-243.6). CONCLUSIONS This work is the first to verify IL-1RN*2 as an independent factor that governs the development of duodenal ulcers. Our data indicate that H. pylori infection and IL-1RN*2 synergistically determine susceptibility to duodenal ulcer. The blood group phenotype is possibly a crucial determinant for the outcome of the impact of an interleukin-1 locus polymorphism on H. pylori-infected individuals.
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Affiliation(s)
- Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
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Basso D, Plebani M. H. pylori infection: bacterial virulence factors and cytokine gene polymorphisms as determinants of infection outcome. Crit Rev Clin Lab Sci 2004; 41:313-37. [PMID: 15307635 DOI: 10.1080/10408360490472804] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The gram negative bacterium H. pylori infects the human stomach worldwide, invariably causing mucosal inflammation. In the majority of cases, H. pylori-associated gastritis remains the only clinical manifestation of the infection, which might cause, otherwise, peptic ulcer, gastric adenocarcinoma. or MALToma. The balance between the bacterial virulence machinery and the host response to the infection determines the different clinical outcomes. The main bacterial virulence factors comprise adhesins (BabA, SabA), the vacuolating cytotoxin VacA, and the products of cag pathogenicity island. The pattern of cytokine production in response to the infection is one of the main host determinants involved in limiting the infection outcome to gastritis or in favoring peptic ulcer or cancer onset. The polymorphisms of some cytokine genes (IL-1beta IL-1RN, TNF-alpha, IFN-gamma) have been correlated with H. pylori-associated gastric adenocarcinoma or peptic ulcer, possibly because they influence the amount of cytokine production in response to H. pylori infection. This review focuses on the role of H. pylori virulence genes and on host cytokines' genes polymorphisms in determining clinical outcome to H. pylori infection.
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Affiliation(s)
- Daniela Basso
- Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy
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Kudo T, Nurgalieva ZZ, Conner ME, Crawford S, Odenbreit S, Haas R, Graham DY, Yamaoka Y. Correlation between Helicobacter pylori OipA protein expression and oipA gene switch status. J Clin Microbiol 2004; 42:2279-81. [PMID: 15131212 PMCID: PMC404672 DOI: 10.1128/jcm.42.5.2279-2281.2004] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Polyclonal antisera to either a synthetic OipA peptide or a recombinant OipA protein detected OipA expression in Helicobacter pylori and correlated with functional oipA status determined by PCR sequence (sensitivity and specificity of >94%). Immunoblotting is a simple and accurate method for detecting expression of the important virulence factor OipA.
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Affiliation(s)
- Takahiko Kudo
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
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