GCKR polymorphism influences liver fat content in patients with type 2 diabetes

Acta Diabetol. 2016 Apr;53(2):237-42. doi: 10.1007/s00592-015-0766-4. Epub 2015 May 16.

Abstract

Aims: It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes.

Methods: Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy.

Results: In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 ± 9.6 vs. 10.3 ± 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01].

Conclusions: This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.

Keywords: 1H-MR spectroscopy; GCKR; Non-alcoholic fatty liver disease; Steatosis; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Alleles
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Heterozygote
  • Humans
  • Lipid Metabolism / genetics*
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Polymorphism, Genetic / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human