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Tabaeian SP, Mahmoudi T, Rezamand G, Nobakht H, Dabiri R, Farahani H, Asadi A, Zali MR. RESISTIN GENE POLYMORPHISM AND NONALCOHOLIC FATTY LIVER DISEASE RISK. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:483-487. [PMID: 36515343 DOI: 10.1590/s0004-2803.202204000-86] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/01/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. METHODS A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. RESULTS NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P<0.001). However, we observed no significant difference in genotype and allele frequencies between the cases with NAFLD and the controls for the RETN rs3745367 polymorphism either before or after adjustment for confounding factors including age, BMI, sex, smoking status, SBP, and DBP. CONCLUSION To our knowledge, this study is the first one that investigated the association between RETN gene rs3745367 variant and biopsy-proven NAFLD. Our findings do not support a role for this gene polymorphism in NAFLD risk in Iranian population; nonetheless, they need to be further investigated in other populations.
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Affiliation(s)
- Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Touraj Mahmoudi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Rezamand
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Nobakht
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Reza Dabiri
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Hamid Farahani
- Department of Physiology and Pharmacology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - 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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Kumar V, Singh J, Aneja A, Singh J. Association of RETN gene polymorphism at +299 G>A with type 2 diabetes mellitus: a meta-analysis. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-019-00746-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
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Liu J, Xing J, Wang B, Wei C, Yang R, Zhu Y, Qiu H. Correlation Between Adiponectin Gene rs1501299 Polymorphism and Nonalcoholic Fatty Liver Disease Susceptibility: A Systematic Review and Meta-Analysis. Med Sci Monit 2019; 25:1078-1086. [PMID: 30735485 PMCID: PMC6376635 DOI: 10.12659/msm.912737] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Metabolic related nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases around the world. A single nucleotide polymorphism (SNP) rs1501299 (+276G>T) in the adiponectin gene has been recently revealed to be responsible for susceptibility to NAFLD. This meta-analysis intended to assess the association risk of NAFLD and rs1501299 polymorphism. Material/Methods We conducted a literature search on PubMed, Embase, and Cochrane Library databases. All involved studies were selected based on our search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Subgroup analysis considered the effects of ethnicity, subject scope, and source of control. Publication bias was assessed by Begg’s tests. Results Eight qualified case-control studies with 1639 patients and 1426 controls demonstrated a significant correlation between rs1501299 polymorphism in adiponectin and NAFLD under the dominant model (OR=1.18, 95% CI=1.02–1.36), allelic contrast (OR=1.21, 95% CI=1.09–1.36), homozygote comparison (OR=1.63, 95% CI=1.26–2.01) and the recessive allele model (OR=1.58, 95% CI=1.23–2.02) with evident heterogeneity. No association was observed between the risk of NAFLD and the genotypic variants in heterozygote comparison (OR=1.11, 95% CI=0.95–1.29) without heterogeneity. Subgroup analysis suggested that the sample size could be the potential source of heterogeneity. Source of control was not the reason for between-study heterogeneity and further sensitivity analysis and publication bias revealed good consistency and symmetry in the pooling studies. Conclusions Results from our current meta-analysis gave insight into the correlation between rs1501299 polymorphism and the risk of NAFLD, indicating the variant of rs1501299 might be related to increased NAFLD susceptibility.
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Affiliation(s)
- Jiaxing Liu
- Bayi College of People's Liberation Army (PLA), Anhui Medical University, Nanjing, Jiangsu, China (mainland)
| | - Jicheng Xing
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Bing Wang
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Changyong Wei
- Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA, USA
| | - Ruining Yang
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Yuerong Zhu
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Hong Qiu
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
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Jiménez-Castro MB, Casillas-Ramírez A, Negrete-Sánchez E, Avalos-de León CG, Gracia-Sancho J, Peralta C. Adipocytokines in Steatotic Liver Surgery/Transplantation. Transplantation 2019; 103:71-77. [PMID: 30586349 DOI: 10.1097/tp.0000000000002098] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Because of the shortage of liver grafts available for transplantation, the restrictions on graft quality have been relaxed, and marginal grafts, such as steatotic livers, are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to I/R injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. After this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice to protect marginal livers subject to I/R injury are presented. Recent strategies based on adipocytokine regulation, which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined.
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Affiliation(s)
| | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria "Bicentenario 2010", Ciudad Victoria, México
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, México
| | - Elsa Negrete-Sánchez
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | | | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Carmen Peralta
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Facultad de Medicina, Universidad International de Cataluña, Barcelona, Spain
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Wang C, Gong J, Wu H. Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease. Biomed Rep 2017; 7:95-104. [PMID: 28804621 DOI: 10.3892/br.2017.926] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 05/12/2017] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease.
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Affiliation(s)
- Chun Wang
- Department of General Surgery, Yongchuan Hospital of Traditional Chinese Medicine, Chongqing 402161, P.R. China
| | - Jianping Gong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China
| | - Hao Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China
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Zayani N, Hamdouni H, Boumaiza I, Achour O, Neffati F, Omezzine A, Najjar MF, Bouslama A. Resistin polymorphims, plasma resistin levels and obesity in Tunisian volunteers. J Clin Lab Anal 2017; 32. [PMID: 28393393 DOI: 10.1002/jcla.22227] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 03/07/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. METHODS We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m2 ) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m2 ). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. RESULTS After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. CONCLUSION The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population.
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Affiliation(s)
- Nesrine Zayani
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Haithem Hamdouni
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Imen Boumaiza
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Ons Achour
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Fadoua Neffati
- Laboratory of Biochemistry and Toxicology, Monastir's University Hospital, Monastir, Tunisia
| | - Asma Omezzine
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
| | - Mohamed Fadhel Najjar
- Laboratory of Biochemistry and Toxicology, Monastir's University Hospital, Monastir, Tunisia
| | - Ali Bouslama
- Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia
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Short article: A randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2017; 29:297-301. [PMID: 27832040 DOI: 10.1097/meg.0000000000000780] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND This study aimed to evaluate the efficacy and safety of sitagliptin for treating Chinese patients with type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). METHODS In total, 72 Chinese T2DM patients with NAFLD were divided randomly into two groups of 36 patients each group. All 72 patients were assigned to receive either sitagliptin or diet and exercise for 52 weeks between January 2013 and December 2015. The outcomes' measurements included serum levels of hemoglobin A1c, fasting plasma glucose, aspartate aminotransferase, and alanine aminotransferase. RESULTS Seventy patients completed the study. Sitagliptin showed greater efficacy than the diet and exercise in decreasing the hemoglobin A1c and fasting plasma glucose levels at weeks 13, 26, 39, and 52. In addition, no significant changes in the average aspartate aminotransferase and alanine aminotransferase levels were found during the 52-week follow-up in both the sitagliptin and the control groups. CONCLUSION The results of this study indicate that sitagliptin is an effective and safe treatment for patients with T2DM and NAFLD.
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Panera N, Della Corte C, Crudele A, Stronati L, Nobili V, Alisi A. Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines. Expert Rev Gastroenterol Hepatol 2016; 10:393-403. [PMID: 26654761 DOI: 10.1586/17474124.2016.1110485] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.
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Affiliation(s)
- Nadia Panera
- a Liver Research Unit , 'Bambino Gesù' Children's Hospital, IRCCS , Rome , Italy
| | - Claudia Della Corte
- b Hepato-Metabolic Disease Unit , 'Bambino Gesù' Children's Hospital, IRCCS , Rome , Italy
| | - Annalisa Crudele
- a Liver Research Unit , 'Bambino Gesù' Children's Hospital, IRCCS , Rome , Italy
| | - Laura Stronati
- c Department of Radiobiology and Human Health , ENEA , Rome , Italy
| | - Valerio Nobili
- b Hepato-Metabolic Disease Unit , 'Bambino Gesù' Children's Hospital, IRCCS , Rome , Italy
| | - Anna Alisi
- a Liver Research Unit , 'Bambino Gesù' Children's Hospital, IRCCS , Rome , Italy
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Yang W, He Y, Liu S, Gan L, Zhang Z, Wang J, Liang J, Dong Y, Wang Q, Hou Z, Yang L. Integrative transcriptomic analysis of NAFLD animal model reveals dysregulated genes and pathways in metabolism. Gene 2016; 595:99-108. [PMID: 27697615 DOI: 10.1016/j.gene.2016.09.047] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 09/26/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023]
Abstract
Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure and hepatocellular carcinoma, which lead to poor long-term prognosis. However, the exact mechanism of development of NAFLD is not well elucidated. In order to better understand the pathogenesis of NAFLD, we have performed an integrative analysis to livers from NAFLD rat models in a global view of the transcriptome. By systemic and integrative analyses, we have found that transport, angiogenesis and cell adhesion were upregulated in response to high fat diet feeding, which may cause a large amount of free fatty acid transport, hepatic fibrosis and hepatocytes injury. GO tree analysis has shown that angiogenesis was upregulated. GO term in response to high fat diet which may cause fibrosis. The pathway interaction network has indicated that upregulated "valine, leucine, and isoleucine metabolism" may decrease the serum concentration of branched-chain amino acid (BCAA). The enhanced degradation of BCAA in NAFLD animal models may lead to inhibition of the regeneration of hepatocytes, reducing the production of albumin, attenuating the inhibition of liver cancer and decreasing immunity. Overall, high fat diet upregulated a variety of metabolism which have converged at TCA cycle. High fatty has pushed the hepatic mitochondria to a "busy state". Comprehensively, genes participated in dysregulated biological process and metabolisms may be served as indicators for evaluation of NAFLD progression and therapeutic targets.
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Affiliation(s)
- Wenhui Yang
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Yan He
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Shijie Liu
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Lulu Gan
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Zhiguo Zhang
- Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, People's Republic of China
| | - Jun Wang
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Jie Liang
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Yang Dong
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Qing Wang
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China
| | - Zongliu Hou
- Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
| | - Li Yang
- Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
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Macaluso FS, Maida M, Petta S. Genetic background in nonalcoholic fatty liver disease: A comprehensive review. World J Gastroenterol 2015; 21:11088-11111. [PMID: 26494964 PMCID: PMC4607907 DOI: 10.3748/wjg.v21.i39.11088] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/11/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.
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Zhang CX, Guo LK, Qin YM, Li GY. Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease. Chin Med J (Engl) 2015; 128:2467-73. [PMID: 26365964 PMCID: PMC4725550 DOI: 10.4103/0366-6999.164931] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. METHODS Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed. RESULTS Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD. CONCLUSION NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.
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Affiliation(s)
- Chao-Xian Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China,Address for correspondence: Prof. Chao-Xian Zhang, Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China E-Mail:
| | - Li-Ke Guo
- Depatment of Stomatology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
| | - Yong-Mei Qin
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
| | - Guang-Yan Li
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
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Giby VG, Ajith TA. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J Hepatol 2014; 6:570-579. [PMID: 25232450 PMCID: PMC4163740 DOI: 10.4254/wjh.v6.i8.570] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 04/29/2014] [Accepted: 05/28/2014] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease (NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evidence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipogenesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transforming growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription factors, namely peroxisome proliferator-activated receptor (PPAR)-α. Recent studies have proposed downregulation of PPAR-α in cases of hepatic steatosis. This review discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.
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Affiliation(s)
- Vettickattuparambil George Giby
- Vettickattuparambil George Giby, Thekkuttuparambil Ananthanarayanan Ajith, Department of Biochemistry, Amala Institute of Medical Sciences, Thrissur-680 555, Kerala, India
| | - Thekkuttuparambil Ananthanarayanan Ajith
- Vettickattuparambil George Giby, Thekkuttuparambil Ananthanarayanan Ajith, Department of Biochemistry, Amala Institute of Medical Sciences, Thrissur-680 555, Kerala, India
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Manti S, Romano C, Chirico V, Filippelli M, Cuppari C, Loddo I, Salpietro C, Arrigo T. Nonalcoholic Fatty liver disease/non-alcoholic steatohepatitis in childhood: endocrine-metabolic "mal-programming". HEPATITIS MONTHLY 2014; 14:e17641. [PMID: 24829591 PMCID: PMC4013495 DOI: 10.5812/hepatmon.17641] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 02/13/2014] [Accepted: 02/19/2014] [Indexed: 02/08/2023]
Abstract
CONTEXT Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. EVIDENCE ACQUISITION A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". RESULTS NAFLD/NASH is probably promoted by "multiple parallel hits": environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. CONCLUSIONS Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.
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Affiliation(s)
- Sara Manti
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Claudio Romano
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Valeria Chirico
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Martina Filippelli
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Italia Loddo
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Carmelo Salpietro
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
| | - Teresa Arrigo
- Department of Pediatric Sciences, Genetics and Pediatric Immunology Unit, University of Messina, Messina, Italy
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