Contribution of Rs780094 and Rs1260326 Polymorphisms in GCKR Gene to Non-alcoholic Fatty Liver Disease: A Meta-Analysis Involving 26,552 Participants

Abstract

Background:: Many published studies attempted to elucidate the implication of glucokinase regulator gene (GCKR) polymorphisms in the susceptibility to nonalcoholic fatty liver disease (NAFLD), but the results among them were still with controversy. Objective:: This meta-analysis aims to precisely assess the relationship between the GCKR polymorphisms and the risk of NAFLD. Methods:: Systematic computerized searches in six databases were performed and updated to April 6, 2020. Meta-analyses were conducted by calling the R programs based on accumulated epidemiological data. Odds ratio (OR) and 95% confidential interval (CI) were calculated to summarize the effect estimates. Results:: In total, 25 studies involving 6,598 cases and 19,954 controls were included. The pooled estimates indicated that the T allele carrier of the GCKR rs780094 polymorphism has predisposition to NAFLD (allele model: OR: 1.20, 95% CI: 1.11~1.29; homozygote model: OR: 1.38, 95% CI: 1.15~1.67; heterozygote model: OR: 1.25, 95% CI: 1.12~1.39; dominant model: OR: 1.29, 95% CI: 1.13~1.47; recessive model: OR: 1.18, 95% CI: 1.06~1.31), and the same as the rs1260326 polymorphism (allele model: OR: 1.32, 95% CI: 1.22~1.42; homozygote model: OR: 1.65, 95% CI: 1.40~1.94; heterozygote model: OR: 1.24, 95% CI: 1.07~1.43; dominant model: OR: 1.39, 95% CI: 1.21~1.59; recessive model: OR: 1.44, 95% CI: 1.28~1.62). Further stratified analyses according to age and ethnicity confirmed the statistical existence in most subgroups. Conclusion:: This meta-analysis suggested that both of the GCKR rs780094 and rs1260326 polymorphisms are significantly associated with the increased risk of NAFLD.

Non-Alcoholic Fatty Liver Disease and Vitamin D in the UK Biobank: A Two-Sample Bidirectional Mendelian Randomisation Study

“…Five SNPs (rs429358, rs3747207, rs9479542, rs10401969 and rs17321515) were associated with NAFLD at p < 5 × 10 −8 in our primary UKBB GWAS. One SNP, rs1260326, related to NAFLD in a previously published study [ 34 ], and with a high LD with rs780094 (r 2 = 0.91) in Speliotes’ study [ 24 ], had an effect estimate in the same direction but with a p = 1.30 × 10 −7 in our study. Although, two SNPs (rs429358 and rs3747207) associated with NAFLD were missing in the SUNLIGHT consortium, we were able to identify only one SNP that could be used as a proxy (rs738408, p = 9 × 10 −42 ) for the SNP (rs3747207) based upon high LD (r 2 = 0.98).…”

Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches

“…Glucokinase regulatory gene (GCKR) is located in chromosome 2p23, expressed in liver tissue, and its protein inhibits glucokinase in hepatocytes [ 217 ]. Rs780094 (T>C) and rs1260326 (T>C/T>G) are two variants that have been identified to be associated with increased risk of NAFLD in various genetic models, with the former variant being more common [ 218 , 219 ]. A proposed mechanism by which rs780094 may predispose to NAFLD is that the variant protein does not exert inhibitory effect on glucokinase, therefore, there is an activation of de novo lipogenesis, TG and cholesterol synthesis [ 220 ].…”

Genetic variants associated with metabolic dysfunction‐associated fatty liver disease in western China

“…And diabetes and fatty liver are often associated 45 . Some studies have identified that GCKR rs1260326 and GCKR rs780094 were significantly associated with MAFLD 11,46 . However, there was no correlation between the GCKR variants and the risk of MAFLD in the study.…”

“… 45 Some studies have identified that GCKR rs1260326 and GCKR rs780094 were significantly associated with MAFLD. 11 , 46 However, there was no correlation between the GCKR variants and the risk of MAFLD in the study. On the other hand, GCKR rs1260326 and GCKR rs780094 were associated with increased TG levels and reduced serum fasting glucose, which was also found in some studies.…”