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Genetic Polymorphisms of PNPLA3 and SAMM50 Are Associated with Nonalcoholic Fatty Liver Disease in a Korean Population

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Background/Aims: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. Methods: We performed a genomewide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. Results: After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p<8.56×10–8) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p<8.56×10–8). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p<2.0×10–10 in the discovery set and p<2.0×10–6 in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p<2.0×10–10 in the discovery set and p<2.0×10–6 in the validation set). Conclusions: We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD.

Abstract

Background/Aims: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. Methods: We performed a genomewide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. Results: After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p<8.56×10–8) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p<8.56×10–8). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p<2.0×10–10 in the discovery set and p<2.0×10–6 in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p<2.0×10–10 in the discovery set and p<2.0×10–6 in the validation set). Conclusions: We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD.

참고문헌 (31)

  1. Vernon G, "Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults", Aliment Pharmacol Ther, 34, pp.274~285 (2011)[DOI]
  2. Ekstedt M, "Long-term follow-up of patients with NAFLD and elevated liver enzymes", Hepatology, 44, pp.865~873 (2006)[DOI]
  3. Adams LA, "The natural history of nonalcoholic fatty liver disease: a population-based cohort study", Gastroenterology, 129, pp.113~121 (2005)[DOI]
  4. Rafiq N, "Long-term follow-up of patients with nonalcoholic fatty liver", Clin Gastroenterol Hepatol, 7, pp.234~238 (2009)[DOI]
  5. Wilfred de Alwis NM, "Genes and nonalcoholic fatty liver disease", Curr Diab Rep, 8, pp.156~163 (2008)[DOI]
  6. Gambino R, "Polymorphism in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH?", Hepatology, 45, pp.1097~1107 (2007)[DOI]
  7. Romeo S, "Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease", Nat Genet, 40, pp.1461~1465 (2008)[DOI]
  8. Sookoian S, "Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease", Hepatology, 53, pp.1883~1894 (2011)[DOI]
  9. Kawaguchi T, "Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese", PLoS One, 7, pp.e38322~ (2012)[DOI]
  10. Kitamoto T, "Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan", Hum Genet, 132, pp.783~792 (2013)[DOI]
  11. Choe EK, "Search for genetic factor association with cancer-free prostate-specific antigen level elevation on the basis of a genome-wide association study in the Korean population", Eur J Cancer Prev (2017)[DOI]
  12. Prati D, "Updated definitions of healthy ranges for serum alanine aminotransferase levels", Ann Intern Med, 137, pp.1~10 (2002)[DOI]
  13. Saadeh S, "The utility of radiological imaging in nonalcoholic fatty liver disease", Gastroenterology, 123, pp.745~750 (2002)[DOI]
  14. Saverymuttu SH, "Ultrasound scanning in the detection of hepatic fibrosis and steatosis", Br Med J (Clin Res Ed), 292, pp.13~15 (1986)[DOI]
  15. Yuan X, "Population-based genomewide association studies reveal six loci influencing plasma levels of liver enzymes", Am J Hum Genet, 83, pp.520~528 (2008)[DOI]
  16. Speliotes EK, "Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits", PLoS Genet, 7, pp.e1001324~ (2011)[DOI]
  17. Mancina RM, "The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent", Gastroenterology, 150, pp.1219~1230 (2016)[DOI]
  18. Chambers JC, "Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma", Nat Genet, 43, pp.1131~1138 (2011)[DOI]
  19. Hotta K, "Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease", BMC Med Genet, 11, pp.172~ (2010)[DOI]
  20. Korean Association for the Study of the Liver (KASL), "KASL clinical practice guidelines: management of nonalcoholic fatty liver disease", Clin Mol Hepatol, 19, pp.325~348 (2013)[DOI]
  21. Chalasani N, "The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology", Gastroenterology, 142, pp.1592~1609 (2012)[DOI]
  22. Schwenzer NF, "Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance", J Hepatol, 51, pp.433~445 (2009)[DOI]
  23. Cruz MA, "Association of the nonalcoholic hepatic steatosis and its degrees with the values of Liver Enzymes and Homeostasis Model Assessment-Insulin Resistance index", Gastroenterology Res, 8, pp.260~264 (2015)[DOI]
  24. Sung KC, "The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects", Atherosclerosis, 203, pp.581~586 (2009)[DOI]
  25. Hernaez R, "Association between variants in or near PNPLA3, GCKR, and PPP1R3B with ultrasounddefined steatosis based on data from the third National Health and Nutrition Examination Survey", Clin Gastroenterol Hepatol, 11, pp.1183~1190 (2013)[DOI]
  26. Palmer CN, "Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant", PLoS One, 7, pp.e39362~ (2012)[DOI]
  27. Krawczyk M, "The common adiponutrin variant p.I148M does not confer gallstone risk but affects fasting glucose and triglyceride levels", J Physiol Pharmacol, 62, pp.369~375 (2011)
  28. Speliotes EK, "PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease", Hepatology, 52, pp.904~912 (2010)[DOI]
  29. Chen L, "Genetic variants in the SAMM50 gene create susceptibility to nonalcoholic fatty liver disease in a Chinese Han population", Hepat Mon, 15, pp.e31076~ (2015)
  30. Chen LZ, "TM6SF2 E167K variant, a novel genetic susceptibility variant, contributing to nonalcoholic fatty liver disease", J Clin Transl Hepatol, 3, pp.265~270 (2015)[DOI]
  31. Mahdessian H, "TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content", Proc Natl Acad Sci U S A, 111, pp.8913~8918 (2014)[DOI]

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