Cargando…
Variation in KCNQ1 is associated with therapeutic response to sulphonylureas
BACKGROUND: We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment. MATERIAL/METHODS: Effect of 6-month sulphony...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539557/ https://www.ncbi.nlm.nih.gov/pubmed/21709633 http://dx.doi.org/10.12659/MSM.881850 |
_version_ | 1782255112302886912 |
---|---|
author | Schroner, Zbynek Dobrikova, Martina Klimcakova, Lucia Javorsky, Martin Zidzik, Jozef Kozarova, Miriam Hudakova, Terezia Tkacova, Ruzena Salagovic, Jan Tkac, Ivan |
author_facet | Schroner, Zbynek Dobrikova, Martina Klimcakova, Lucia Javorsky, Martin Zidzik, Jozef Kozarova, Miriam Hudakova, Terezia Tkacova, Ruzena Salagovic, Jan Tkac, Ivan |
author_sort | Schroner, Zbynek |
collection | PubMed |
description | BACKGROUND: We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment. MATERIAL/METHODS: Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe. RESULTS: The reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95±0.13 vs. 7.50±0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58±0.13 vs. 1.04±0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R(2)=0.48). CONCLUSIONS: Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype. |
format | Online Article Text |
id | pubmed-3539557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-35395572013-04-24 Variation in KCNQ1 is associated with therapeutic response to sulphonylureas Schroner, Zbynek Dobrikova, Martina Klimcakova, Lucia Javorsky, Martin Zidzik, Jozef Kozarova, Miriam Hudakova, Terezia Tkacova, Ruzena Salagovic, Jan Tkac, Ivan Med Sci Monit Clinical Research BACKGROUND: We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment. MATERIAL/METHODS: Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe. RESULTS: The reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95±0.13 vs. 7.50±0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58±0.13 vs. 1.04±0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R(2)=0.48). CONCLUSIONS: Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype. International Scientific Literature, Inc. 2011-07-01 /pmc/articles/PMC3539557/ /pubmed/21709633 http://dx.doi.org/10.12659/MSM.881850 Text en © Med Sci Monit, 2011 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. |
spellingShingle | Clinical Research Schroner, Zbynek Dobrikova, Martina Klimcakova, Lucia Javorsky, Martin Zidzik, Jozef Kozarova, Miriam Hudakova, Terezia Tkacova, Ruzena Salagovic, Jan Tkac, Ivan Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title | Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title_full | Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title_fullStr | Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title_full_unstemmed | Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title_short | Variation in KCNQ1 is associated with therapeutic response to sulphonylureas |
title_sort | variation in kcnq1 is associated with therapeutic response to sulphonylureas |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539557/ https://www.ncbi.nlm.nih.gov/pubmed/21709633 http://dx.doi.org/10.12659/MSM.881850 |
work_keys_str_mv | AT schronerzbynek variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT dobrikovamartina variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT klimcakovalucia variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT javorskymartin variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT zidzikjozef variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT kozarovamiriam variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT hudakovaterezia variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT tkacovaruzena variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT salagovicjan variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas AT tkacivan variationinkcnq1isassociatedwiththerapeuticresponsetosulphonylureas |