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

Gut Liver. 2018 May 15;12(3):316-323. doi: 10.5009/gnl17306.

Abstract

Background/aims: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors.

Methods: We performed a genome-wide 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.

Keywords: Genome-wide association study; Non-alcoholic fatty liver disease; Polymorphism, single nucleotide.

MeSH terms

  • Age Factors
  • Alanine Transaminase / metabolism
  • Body Mass Index
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium / genetics
  • Lipase / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins / genetics*
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / ethnology
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Republic of Korea / ethnology
  • Risk Factors

Substances

  • Membrane Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins
  • SAMM50 protein, human
  • Alanine Transaminase
  • Lipase
  • adiponutrin, human