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Malmquist M, Rabe H, Malmborg P, Gale G, Ideström M, Sigurdsson GV, Hasséus B, Wold AE, Saalman R. Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis. Dig Dis Sci 2023:10.1007/s10620-023-07821-8. [PMID: 36646935 DOI: 10.1007/s10620-023-07821-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 01/01/2023] [Indexed: 01/18/2023]
Abstract
BACKGROUND Orofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis. AIMS The aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD. METHODS Clinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG. RESULTS The clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01). CONCLUSION The results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.
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Affiliation(s)
- Marianne Malmquist
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
- Department of Pediatrics, The Central Hospital of Växjö, Strandvägen 8, 352 34, Växjö, Sweden.
| | - Hardis Rabe
- Department of Infectious Disease, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Petter Malmborg
- Sachsska Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Gita Gale
- Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Maja Ideström
- Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatric Medicine, Uppsala University Children's Hospital, Uppsala, Sweden
| | - Gudmundur Vignir Sigurdsson
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Bengt Hasséus
- Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Agnes E Wold
- Department of Infectious Disease, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Robert Saalman
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
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Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of Vitamin D in Inflammatory Bowel Disease. Nutr Clin Pract 2016; 32:337-345. [PMID: 28537516 DOI: 10.1177/0884533616674492] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Vitamin D is a secosteroid hormone that possesses immunomodulatory properties and has been demonstrated to potentially influence inflammatory bowel disease (IBD) pathogenesis and activity. Epidemiologic data have associated vitamin D deficiency with an increased risk of IBD, hospitalizations, surgery, and loss of response to biologic therapy. Conversely, IBD itself can lead to vitamin D deficiency. This bidirectional relationship between vitamin D and IBD suggests the need for monitoring and repletion of vitamin D, as needed, in the IBD patient. This review discusses the role of vitamin D in IBD and provides practical guidance on vitamin D repletion.
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Affiliation(s)
- Berkeley N Limketkai
- 1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.,2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Gerard E Mullin
- 2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David Limsui
- 1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Alyssa M Parian
- 2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Moller FT, Knudsen L, Harbord M, Satsangi J, Gordon H, Christiansen L, Christensen K, Jess T, Andersen V. Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity. World J Gastroenterol 2016; 22:5050-5059. [PMID: 27275097 PMCID: PMC4886380 DOI: 10.3748/wjg.v22.i21.5050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 03/21/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.
METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.
RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.
CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.
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Does Crohn's Disease with Concomitant Orofacial Granulomatosis Represent a Distinctive Disease Subtype? Inflamm Bowel Dis 2016; 22:1071-7. [PMID: 26829409 DOI: 10.1097/mib.0000000000000670] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although orofacial granulomatosis (OFG) may present as a separate clinical entity, it often seems in conjunction with various systemic diseases, of which Crohn's disease (CD) is one of the most common. The aim of this study was to investigate whether CD with concomitant OFG represents a distinctive disease subtype. METHODS Twenty-one patients with CD and concomitant OFG (CD+OFG group) were included in the study. As the reference group, a cohort of 39 patients with CD but without OFG (CD-R group) was used. Demographic data and clinical characteristics were recorded at the time of diagnosis. The 2 groups were compared using multivariate analyses. RESULTS The percentage of patients with intestinal inflammation in the upper gastrointestinal tract was significantly higher in the CD+OFG group, as compared with the CD-R group (81% versus 33%; P < 0.001). Furthermore, ileocolonic inflammation was significantly more common in the CD+OFG patients (81% versus 46%; P = 0.013). In addition, perianal disease was more frequently observed in the CD+OFG group (48% versus 18%; P = 0.033). Significantly more patients showed evidence of granulomas in the primary endoscopy in the CD+OFG group than in the CD-R group (81% versus 38%; P = 0.003). CONCLUSION The data from this study suggest that the presence of CD in conjunction with OFG represents a distinctive subphenotype of CD that is characterized by extensive inflammation, perianal disease, and pronounced granuloma formation in the intestine.
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Klotz C, Dhooge M, Oudjit A, Barret M, Beuvon F, Chaussade S, Coriat R, Abitbol V. Prise en charge de la maladie de Crohn. Presse Med 2015; 44:411-7. [DOI: 10.1016/j.lpm.2014.07.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Revised: 07/15/2014] [Accepted: 07/28/2014] [Indexed: 11/16/2022] Open
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Sahu KK, Minz S, Kaurav M, Pandey RS. Proteins and peptides: The need to improve them as promising therapeutics for ulcerative colitis. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2014; 44:642-53. [PMID: 25379956 DOI: 10.3109/21691401.2014.975239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The present review briefly describes the nature, type and pathogenesis of ulcerative colitis, and explores the potential use of peptides and proteins in the treatment of inflammatory bowel disease, especially ulcerative colitis. Intestinal absorption and the barrier mechanism of peptide and protein drugs are also discussed, with special emphasis on various strategies which make these drugs better therapeutics having high specificity, potency and molecular targeting ability. However, the limitation of such therapeutics are oral administration, poor pharmacokinetic profile and decreased bioavailability. The recent findings illustrated in this review will be helpful in designing the peptide/protein drugs as a promising treatment of choice for ulcerative colitis.
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Affiliation(s)
- Kantrol Kumar Sahu
- a Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya , Bilaspur, C.G. , India
| | - Sunita Minz
- a Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya , Bilaspur, C.G. , India
| | - Monika Kaurav
- a Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya , Bilaspur, C.G. , India
| | - Ravi Shankar Pandey
- a Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya , Bilaspur, C.G. , India
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Nunes T, Fiorino G, Danese S, Sans M. Familial aggregation in inflammatory bowel disease: Is it genes or environment? World J Gastroenterol 2011; 17:2715-22. [PMID: 21734779 PMCID: PMC3123468 DOI: 10.3748/wjg.v17.i22.2715] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2010] [Revised: 09/18/2010] [Accepted: 09/25/2010] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.
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Brest P, Corcelle E, Cesaro A, Chargui A, Belaïd A, Klionsky D, Vouret-Craviari V, Hebuterne X, Hofman P, Mograbi B. Autophagy and Crohn's disease: at the crossroads of infection, inflammation, immunity, and cancer. Curr Mol Med 2010; 10:486-502. [PMID: 20540703 PMCID: PMC3655526 DOI: 10.2174/156652410791608252] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2009] [Accepted: 11/13/2009] [Indexed: 12/11/2022]
Abstract
Inflammatory bowel diseases (IBD) are common inflammatory disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD are high in North America and Europe, affecting as many as one in 500 people. These diseases are associated with high morbidity and mortality. Colorectal cancer risk is also increased in IBD, correlating with inflammation severity and duration. IBD are now recognized as complex multigenetic disorders involving at least 32 different risk loci. In 2007, two different autophagy-related genes, ATG16L1 (autophagy-related gene 16-like 1) and IRGM (immunity-related GTPase M) were shown to be specifically involved in CD susceptibility by three independent genome-wide association studies. Soon afterwards, more than forty studies confirmed the involvement of ATG16L1 and IRGM variants in CD susceptibility and gave new information on the importance of macroautophagy (hereafter referred to as autophagy) in the control of infection, inflammation, immunity and cancer. In this review, we discuss how such findings have undoubtedly changed our understanding of CD pathogenesis. A unifying autophagy model then emerges that may help in understanding the development of CD from bacterial infection, to inflammation and finally cancer. The Pandora's box is now open, releasing a wave of hope for new therapeutic strategies in treating Crohn's disease.
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Affiliation(s)
- P. Brest
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
| | - E.A. Corcelle
- Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
| | - A. Cesaro
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
| | - A. Chargui
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
| | - A. Belaïd
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
| | - D.J. Klionsky
- University of Michigan, Life Sciences Institute, Ann Arbor, Michigan, USA
| | - V. Vouret-Craviari
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
| | - X. Hebuterne
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
- Centre Hospitalier Universitaire de Nice, Pôle Digestif, Hôpital L'Archet II, Nice, France
| | - P. Hofman
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
- Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France
| | - B. Mograbi
- Inserm ERI-21/EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France
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Queiroz DMM, Oliveira AG, Saraiva IEB, Rocha GA, Rocha AMC, das Graças Pimenta Sanna M, Guerra JB, Dani R, Ferrari MDLA, Castro LPF. Immune response and gene polymorphism profiles in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2009; 15:353-8. [PMID: 18942754 DOI: 10.1002/ibd.20757] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Polymorphisms in genes linked to the innate and adaptive immune response may be involved in inflammatory bowel disease pathogenesis. Our aim was to investigate associations among IL1B-511, IL1B-31, IL1RN, TNFA-307, TLR-2, TLR-4, IL2-330, NOD2 G908R, NOD2 L1007fsinsC polymorphisms and both Crohn's disease (CD) and ulcerative colitis (UC) in a Brazilian population. METHODS We studied 43 patients with CD, 42 with UC, and 541 blood donors. Polymorphisms were evaluated by PCR, PCR-CTPP, or PCR-RFLP. Data were analyzed in multivariate models adjusting for confounding factors. RESULTS IL1RN VNTR (P = 0.00, odds ratio [OR] = 2.43, 95% confidence interval [CI] = 1.50-3.90), as well as TNFA-307 polymorphic allele (P = 0.05, OR = 1.70, 95% CI = 1.00-2.94) were associated with UC. Both NOD2 mutations (G908R, P = 0.02, OR = 6.83, 95% CI = 1.62-25.45, and L1007fsinsC, P = 0.00, OR = 20.00, 95% CI = 3.21-124.69) were associated with CD. CONCLUSIONS Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA-307 loci and UC, as well as polymorphisms in the NOD2 gene and CD. These results highlight the importance of different genetic profiles associated with CD and UC.
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Peña AS. Why are genetic studies important in IBD? Inflamm Bowel Dis 2008; 14 Suppl 2:S79-80. [PMID: 18816776 DOI: 10.1002/ibd.20676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- A S Peña
- Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands
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Ernst A, Jacobsen B, Østergaard M, Okkels H, Andersen V, Dagiliene E, Pedersen IS, Thorsgaard N, Drewes AM, Krarup HB. Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population. Scand J Gastroenterol 2007; 42:1445-51. [PMID: 17852840 DOI: 10.1080/00365520701427102] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark. MATERIAL AND METHODS Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined. RESULTS Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene-dosage effect was observed (ORadj.smoking 22.2; p <0.001 for carrying two CARD15 mutations versus ORadj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (ORadj.smoking 3.6; p <0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p <0.001), but no multiplicative effect of smoking on CARD15 genotypes was found. CONCLUSIONS In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future.
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Affiliation(s)
- Anja Ernst
- Department of Clinical Biochemistry, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
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Ferguson LR, Shelling AN, Browning BL, Huebner C, Petermann I. Genes, diet and inflammatory bowel disease. Mutat Res 2007; 622:70-83. [PMID: 17628615 DOI: 10.1016/j.mrfmmm.2007.05.011] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2006] [Revised: 04/30/2007] [Accepted: 05/23/2007] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) arises in part from a genetic predisposition, through the inheritance of a number of contributory genetic polymorphisms. These variant forms of genes may be associated with an abnormal response to normal luminal bacteria. A consistent observation across most populations is that any of three polymorphisms of the Caspase-activated recruitment domain (CARD15) gene are more prevalent in IBD patients as compared with unaffected controls. Similar aberrant responses to bacteria are associated with variants in Autophagy-related 16-like 1 (ATG16L1) and human defensin (HBD-2, -3 and -4) genes. The defective bacterial signal in turn leads to an excessive immune response, presenting as chronic gut inflammation in susceptible individuals. Inconsistent population reports implicate the major histocompatability complex (MHC), that encodes a number of human leukocyte antigens (HLA), MHC class I chain-related gene A (MICA) or cytokines, such as tumour necrosis factor-alpha (TNF-alpha). Toll-like receptors encoded by the TLR4 or TLR9 genes may also play a role. Recent whole genome scans suggest that a rare variant in the interleukin-23 receptor (IL23R) gene may actually protect against IBD. Other implicated genes may affect mucosal cell polarity (Drosophila discs large homologue 5, DLG5) or mucosal transporter function (sodium dependent organic cation transporters, SLC22A4 and SLC22A5). A variant in ABCB1 (ATP-binding cassette subfamily B member 1) may be especially associated with increased risk of UC. While pharmacogenetics is increasingly being used to predict and optimise clinical response to therapy, nutrigenetics may have even greater potential. In many cases, IBD can be controlled through prescribing an elemental diet, which appears to act through modulating cytokine response and changing the gut microbiota. More generally, no single group of dietary items is beneficial or detrimental to all patients, and elimination diets have been used to individualise dietary requirements. However, recognising the nature of the genes involved may suggest a more strategic approach. Pro- or prebiotics will directly influence the microbial flora, while immunonutrition, including omega-3 fatty acids and certain polyphenols, may reduce the symptoms of gut inflammation. The expression of gut transporters may be modulated through various herbal remedies including green tea polyphenols. Such approaches would require that the gene of interest is functioning normally, other than its expression being up or down-regulated. However, new approaches are being developed to overcome the effects of polymorphisms that affect the function of a gene. A combination of human correlation studies with experimental models could provide a rational strategy for optimising nutrigenetic approaches to IBD.
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Affiliation(s)
- Lynnette R Ferguson
- Discipline of Nutrition, Faculty of Medical & Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
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Abstract
Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory autoimmune conditions of the gastrointestinal tract. Other organs, such as the eyes, skin and articulations, are often affected and IBD may be accompanied by other diseases of autoimmune origin. There is no single etiological factor responsible for the onset of IBD. Recent advances in genetics and in the molecular mechanisms of the proteins coded by these genes have given rise to a new vision in understanding these complex diseases. Activation of specific genes that affect antigen presentation and the handling of cells by innate immunity may lead to autoimmunity with the consequent activation of the major histocompatibility complex (MHC) and multiple cytokines involved in the regulation of acquired immunity. In this review IBD is described as a constellation of diseases that can best be classified as barrier diseases. This vision, developed by Kiel in Germany, includes the idea that changes in our environment due to the westernization of civilization have not been met with adaptation of the innate immune system, and this has given rise to autoimmune diseases. These diseases affect 1-5 of 1000 individuals and represent a major burden on the national health systems of many countries on different continents. On a world scale, a major challenge is to generate interventions to prevent the development of these diseases in Asia, Latin America and Africa.
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Affiliation(s)
- A S Peña
- VU University Medical Centre, Head, Department of Gastroenterology, 1007 MB Amsterdam, The Netherlands.
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Halme L, Paavola-Sakki P, Turunen U, Lappalainen M, Farkkila M, Kontula K. Family and twin studies in inflammatory bowel disease. World J Gastroenterol 2006; 12:3668-72. [PMID: 16773682 PMCID: PMC4087458 DOI: 10.3748/wjg.v12.i23.3668] [Citation(s) in RCA: 191] [Impact Index Per Article: 10.1] [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
Studies examining the inheritance of inflammatory bowel disease (IBD) within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn’s disease (CD) is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis (UC) and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.
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Affiliation(s)
- Leena Halme
- Department of Transplantation and Liver Surgery, Helsinki University Hospital, Finland.
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