Gene Polymorphism is Associated with Obesity and Non-alcoholic Fatty Liver Disease in the Han Chinese

Klotho beta (KLB) mediates binding of fibroblast growth factor (FGF) 21 to the FGF receptor (FGFR). FGF21-KLB-FGFR signaling regulates multiple metabolic systems in the liver, and we hypothesized that , and single-nucleotide polymorphisms (SNPs) are involved in hepatic lipid accumulation. The SNPs were detected in 1688 individuals divided into four groups: non-obese without non-alcoholic fatty liver disease (NAFLD), obese without NAFLD, non-obese with NAFLD, and obese with NAFLD. The A-allele of SNP rs7670903 correlated with higher body mass index ( = 0.0005), and the A-allele frequency was higher in the obese than non-obese group ( = 0.003). The G-allele frequency of rs7674434 and T-allele frequency of rs12152703 were higher in the obese with NAFLD than obese without NAFLD group ( = 0.004 and = 0.006), but the genotype distribution between two non-obese groups did not differ. rs7674434 and rs12152703 had associations with alanine aminotransferase (ALT) ( = 0.03 and = 0.04, respectively) and gamma-glutamyltransferase ( = 0.03 and = 0.02, respectively) levels in all subjects, but the associations were especially strong with ALT in the NAFLD group ( = 0.005 and = 0.008, respectively). These findings suggest that SNPs are related to obesity and hepatic inflammation and that they may be involved in the pathogenesis of NAFLD.