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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, PRC.
authors.forename: Fazhong
authors.initials: F
authors.lastname: He
authors.forename: Jianquan
authors.initials: J
authors.lastname: Luo
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Luo
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Yijing
authors.initials: Y
authors.lastname: He
authors.forename: Dingliang
authors.initials: D
authors.lastname: Zhu
authors.forename: Jinping
authors.initials: J
authors.lastname: Gao
authors.forename: Sheng
authors.initials: S
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Qian
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002681:China; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D018674:Adrenergic Antagonists; D015415:Biomarkers; D002121:Calcium Channel Blockers; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human