GCKR Variants Increase Triglycerides While Protecting from Insulin Resistance in Chinese Children

BACKGROUND: Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. METHODS AND RESULTS: We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (p<0.05). In children, both variants significantly reduced insulin (p<0.05. for rs1260326, β = −0.07; for rs1260333, β = −0.07) and HOMA-IR (p<0.05. for rs1260326, β = −0.03; for rs1260333, β = −0.03). There were significant associations between two variants and insulin resistance for children. Under co-dominant model, for CT vs. CC, OR is 0.83 (95%CI 0.69–1.00) for rs1260326, and 0.83 (95%CI 0.68–1.00) for rs1260333; for TT vs. CC, OR is 0.72 (95%CI 0.58–0.88) for rs1260326, and 0.72 (95%CI 0.58–0.89) for rs1260333. Under allele model, for allele T vs. C, the ORs are 0.85 (95%CI 0.76–0.94) and 0.85 (95%CI 0.76–0.94) for rs1260326 and rs1260333, respectively). CONCLUSIONS: Our study confirmed the associations between GCKR variants and triglycerides in Chinese children and adults. Triglycerides-increasing alleles of GCKR variants reduce insulin and HOMA-IR index, and protect from insulin resistance in children. Our results suggested GCKR has an effect on development of insulin resistance in Chinese children.