Association betweenTCF7L2Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide

[摘要] Previous studies showed associations between variants inTCF7L2gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compareTCF7L2genotype specific effect of gliclazide binding toKATPchannel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment.TCF7L2rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32±0.15% versus0.73±0.11%,Padj=0.005).No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only theTCF7L2genotype (P=0.006) and the baseline HbA1c (P<0.001) were significant predictors of ΔHbA1c.After introducing an interaction term between theTCF7L2genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P=0.023) of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among theTCF7L2genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.

[学科分类] 内分泌与代谢学