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The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China

BACKGROUND: KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are...

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Autores principales: He, Fazhong, Luo, Jianquan, Luo, Zhiying, Fan, Lan, He, Yijing, Zhu, Dingliang, Gao, Jinping, Deng, Sheng, Wang, Yan, Qian, Yuesheng, Zhou, Honghao, Chen, Xiaoping, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632552/
https://www.ncbi.nlm.nih.gov/pubmed/23613831
http://dx.doi.org/10.1371/journal.pone.0061317
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author He, Fazhong
Luo, Jianquan
Luo, Zhiying
Fan, Lan
He, Yijing
Zhu, Dingliang
Gao, Jinping
Deng, Sheng
Wang, Yan
Qian, Yuesheng
Zhou, Honghao
Chen, Xiaoping
Zhang, Wei
author_facet He, Fazhong
Luo, Jianquan
Luo, Zhiying
Fan, Lan
He, Yijing
Zhu, Dingliang
Gao, Jinping
Deng, Sheng
Wang, Yan
Qian, Yuesheng
Zhou, Honghao
Chen, Xiaoping
Zhang, Wei
author_sort He, Fazhong
collection PubMed
description BACKGROUND: KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. MATERIALS AND METHODS: To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. RESULTS: There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. CONCLUSION: We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs.
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spelling pubmed-36325522013-04-23 The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China He, Fazhong Luo, Jianquan Luo, Zhiying Fan, Lan He, Yijing Zhu, Dingliang Gao, Jinping Deng, Sheng Wang, Yan Qian, Yuesheng Zhou, Honghao Chen, Xiaoping Zhang, Wei PLoS One Research Article BACKGROUND: KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. MATERIALS AND METHODS: To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. RESULTS: There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. CONCLUSION: We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs. Public Library of Science 2013-04-22 /pmc/articles/PMC3632552/ /pubmed/23613831 http://dx.doi.org/10.1371/journal.pone.0061317 Text en © 2013 He et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
He, Fazhong
Luo, Jianquan
Luo, Zhiying
Fan, Lan
He, Yijing
Zhu, Dingliang
Gao, Jinping
Deng, Sheng
Wang, Yan
Qian, Yuesheng
Zhou, Honghao
Chen, Xiaoping
Zhang, Wei
The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title_full The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title_fullStr The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title_full_unstemmed The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title_short The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
title_sort kcnh2 genetic polymorphism (1956, c>t) is a novel biomarker that is associated with ccb and α,β-adr blocker response in eh patients in china
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632552/
https://www.ncbi.nlm.nih.gov/pubmed/23613831
http://dx.doi.org/10.1371/journal.pone.0061317
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