title: Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.
abstract: 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%, P (adj) = 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.
authors.affiliation: Department of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Javorský
authors.forename: Eva
authors.initials: E
authors.lastname: Babjaková
authors.forename: Lucia
authors.initials: L
authors.lastname: Klimčáková
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Schroner
authors.forename: Jozef
authors.initials: J
authors.lastname: Zidzik
authors.forename: Mária
authors.initials: M
authors.lastname: Stolfová
authors.forename: Ján
authors.initials: J
authors.lastname: Salagovič
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkáč