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

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 (K(ATP)) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of...

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Autores principales: Javorský, Martin, Babjaková, Eva, Klimčáková, Lucia, Schroner, Zbynek, Židzik, Jozef, Štolfová, Mária, Šalagovič, Ján, Tkáč, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590634/
https://www.ncbi.nlm.nih.gov/pubmed/23509454
http://dx.doi.org/10.1155/2013/374858
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author Javorský, Martin
Babjaková, Eva
Klimčáková, Lucia
Schroner, Zbynek
Židzik, Jozef
Štolfová, Mária
Šalagovič, Ján
Tkáč, Ivan
author_facet Javorský, Martin
Babjaková, Eva
Klimčáková, Lucia
Schroner, Zbynek
Židzik, Jozef
Štolfová, Mária
Šalagovič, Ján
Tkáč, Ivan
author_sort Javorský, Martin
collection PubMed
description 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 (K(ATP)) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to K(ATP) 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.
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spelling pubmed-35906342013-03-18 Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide Javorský, Martin Babjaková, Eva Klimčáková, Lucia Schroner, Zbynek Židzik, Jozef Štolfová, Mária Šalagovič, Ján Tkáč, Ivan Int J Endocrinol Clinical Study 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 (K(ATP)) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to K(ATP) 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. Hindawi Publishing Corporation 2013 2013-02-20 /pmc/articles/PMC3590634/ /pubmed/23509454 http://dx.doi.org/10.1155/2013/374858 Text en Copyright © 2013 Martin Javorský et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Study
Javorský, Martin
Babjaková, Eva
Klimčáková, Lucia
Schroner, Zbynek
Židzik, Jozef
Štolfová, Mária
Šalagovič, Ján
Tkáč, Ivan
Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title_full Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title_fullStr Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title_full_unstemmed Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title_short Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
title_sort association between tcf7l2 genotype and glycemic control in diabetic patients treated with gliclazide
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590634/
https://www.ncbi.nlm.nih.gov/pubmed/23509454
http://dx.doi.org/10.1155/2013/374858
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