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

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.