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

Role of hepatokines in non-alcoholic fatty liver disease

“…GWAS revealed that SNPs of Fgf21 was associated with the pathogenesis of NFALD. [31] Further studies found that serum FGF21 was elevated in patients with NAFLD verified by MRI or ultrasonography. [26,[32][33][34] Serum FGF21 level was positively correlated with hepatic liver fraction indicated by MRI and liver triglycerides content indicated by biopsy.…”

The role of FGF21 and its analogs on liver associated diseases

“…While FGF21 can affect the pathomechanism of these diseases, it can also play an important role as a biomarker for NAFLD and AFLD and show significant results in curing fatty liver and metabolic associated diseases. In a study done on a Han Chinese non-diabetic population the association of four Single Nucleotide Polymorphisms (SNPs) with NAFLD was investigated ( 45 ). They found that rs499765 was associated with serum levels of FGF21 and can be a predicting factor for measuring the risk of NAFLD ( 45 ).…”

“…In a study done on a Han Chinese non-diabetic population the association of four Single Nucleotide Polymorphisms (SNPs) with NAFLD was investigated ( 45 ). They found that rs499765 was associated with serum levels of FGF21 and can be a predicting factor for measuring the risk of NAFLD ( 45 ). Besides, they found that rs2071699 and rs838136 correlate with aspartate aminotransferase serum concentration and rs838136 is associated with alanine aminotransferase levels ( 45 ).…”

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers

“…However, a minimal amount of data concerning Brazilian T2D patients can be found [ 15 ]. The single nucleotide polymorphism (SNP) rs499765 C > G in the FGF21 gene was found to be associated with serum FGF21 levels and NAFLD in a Chinese nondiabetic population [ 16 ], but no data in T2D patients with NAFLD are currently available.…”