Research Paper Volume 11, Issue 18 pp 7847—7858

KLB gene polymorphism is associated with obesity and non-alcoholic fatty liver disease in the Han Chinese

Fang Ji 1, 2, *, , Ye Liu 3, *, , Jun-Gui Hao 2, , Li-Ping Wang 2, , Ming-Jia Dai 2, , Gui-Fang Shen 4, , Xue-Bing Yan 1, 2, ,

  • 1 Department of Infectious Diseases, Nanjing Medical University, Nanjing, Jiangsu, China
  • 2 Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
  • 3 Department of Infectious Disease, Xuzhou Medical University, Xuzhou, Jiangsu, China
  • 4 Department of Physical Examination Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
* Equal contribution

received: June 20, 2019 ; accepted: September 14, 2019 ; published: September 23, 2019 ;

https://doi.org/10.18632/aging.102293
How to Cite

Copyright © 2019 Ji et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 FGF21, KLB and FGFR 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 KLB SNP rs7670903 correlated with higher body mass index (P = 0.0005), and the A-allele frequency was higher in the obese than non-obese group (P = 0.003). The G-allele frequency of KLB rs7674434 and T-allele frequency of rs12152703 were higher in the obese with NAFLD than obese without NAFLD group (P = 0.004 and P = 0.006), but the genotype distribution between two non-obese groups did not differ. KLB rs7674434 and rs12152703 had associations with alanine aminotransferase (ALT) (P = 0.03 and P = 0.04, respectively) and gamma-glutamyltransferase (P = 0.03 and P = 0.02, respectively) levels in all subjects, but the associations were especially strong with ALT in the NAFLD group (P = 0.005 and P = 0.008, respectively). These findings suggest that KLB SNPs are related to obesity and hepatic inflammation and that they may be involved in the pathogenesis of NAFLD.

Abbreviations

ALT: Alanine aminotransferase; Chr: Chromosome; FGF: Fibroblast growth factor; HWE: Hardy–Weinberg equilibrium; KLB: Klotho beta; LD: Linkage disequilibrium; LDL-C: Low-density lipoprotein cholesterol; MAF: Minor allele frequency; NAFLD: Non-alcoholic fatty liver disease; SNPs: Single-nucleotide polymorphisms; γ-GT: Gamma-glutamyltransferase.