Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide

• Main Authors: Martin Javorský, Eva Babjaková, Lucia Klimčáková, Zbynek Schroner, Jozef Židzik, Mária Štolfová, Ján Šalagovič, Ivan Tkáč
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: International Journal of Endocrinology
• Online Access: http://dx.doi.org/10.1155/2013/374858
• ISSN: 1687-8337; 1687-8345

Previous studies showed associations between variants in TCF7L2 gene 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 compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel 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. TCF7L2 rs7903146 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% versus 0.73±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 the TCF7L2 genotype (P=0.006) and the baseline HbA1c (P<0.001) were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype 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 the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.