Associations of common polymorphisms in GCKR with metabolic syndrome

Background: Metabolic syndrome (MetS) is characterized by a combination of cardio-metabolic risk factors. Given that genetic factors have been shown to contribute to individual susceptibility to MetS, the identification of genetic markers for disease risk is essential. Recent studies revealed that rs780094 and rs1260326 of glucokinase regulatory gene (GCKR) are associated with serum triglycerides, plasma glucose levels and metabolic syndrome. The aim of this study was to investigate associations of GCKR gene variants with metabolic syndrome and its components. Methods: This case-control study was conducted from April to August 2017. In this study, 8710 adults (3522 males and 5188 females), over 19 years, were randomly selected from the Tehran Lipid and Glucose Study (TLGS) population. Based on joint interim statement (JIS) criteria, the subjects were divided into two groups: case and control. Genotyping was performed by HumanOmniExpress-24 v1.0 BeadChips (Illumina, San Diego, CA, USA). Results: Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Comparisons of allele frequencies by the Chi-square test revealed that frequencies of TT genotype of both polymorphisms were significantly higher among patient group than healthy group. Logistic regression analysis with adjustment for age, gender and CRP revealed that the GCKR polymorphisms (rs1260326: odds ratio 2.7, 95% CI 1.6-4.6, rs780094: odds ratio 2.5, 95% CI 1.5-4.2) were significantly associated with MetS. Frequency of TT genotype was more in persons who had C-reactive protein (CRP) levels above 3 mg/l. The minor T allele of both polymorphisms was significantly associated with increases in the blood serum concentration triglyceride and to a decrease in fasting plasma glucose levels. Conclusion: The results of our study indicated that, rs780094 and rs1260326 common polymorphisms of the GCKR gene were associated with serum triglycerides levels, fasting plasma glucose levels, and metabolic syndrome in a sample of the Tehranian population (TLGS), as it was already confirmed the inverse effect of this polymorphisms on triglycerides and glucose levels in previous studies.