The Single Nucleotide Polymorphism rs499765 Is Associated with Fibroblast Growth Factor 21 and Nonalcoholic Fatty Liver Disease in a Chinese Population with Normal Glucose Tolerance

Abstract

Background: Fibroblast growth factor 21 (FGF21) is a hormone involved in the metabolism of carbohydrates and lipids. Increased circulating FGF21 levels are closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association between genetic variations of FGF21 and NAFLD remains unknown. In our study, we aimed to investigate the association of these genetic variations with serum FGF21 levels and NAFLD. Methods: We genotyped four single nucleotide polymorphisms (SNPs) in FGF21 and its flanking region in 340 nondiabetic subjects. NAFLD was defined as the presence of a specific abdominal ultrasonographic pattern. Serum FGF21 concentrations were measured using an enzyme-linked immunosorbent assay kit. Results: We found significant evidence of an association with NAFLD for rs499765 (p = 0.039). After adjusting for age and sex, the effect of rs499765 on NAFLD remained significant (p = 0.045). However, after adjusting for multiple comparisons, no association was found. Moreover, rs499765 was associated with serum FGF21 levels (p = 0.030). In addition, both rs2071699 and rs838136 showed an association with serum aspartate aminotransferase levels (p = 0.049 and p = 0.047, respectively). The SNP rs838136 also showed a correlation with serum alanine aminotransferase concentrations after adjustment for body mass index (p = 0.034). We also combined the minor group with the heterozygous genotype and observed that rs499765 had an effect on FGF21 (p = 0.031). Conclusion: The variant rs499765 adjacent to FGF21 is associated with serum FGF21 levels and NAFLD in a Chinese nondiabetic population. © 2014 S. Karger AG, Basel