WNK1/WNK4 相关的高血压多态性与氢氯噻嗪的反应无关。

Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response.

机构信息

Department of Geriatrics, The Military General Hospital of Beijing PLA, Beijing, China; Hypertension Division, Department of Cardiology, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.

Hypertension Division, Department of Cardiology, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.

出版信息

Clin Biochem. 2011 Sep;44(13):1045-1049. doi: 10.1016/j.clinbiochem.2011.06.008. Epub 2011 Jun 17.

DOI:10.1016/j.clinbiochem.2011.06.008

PMID:21704025

Abstract

OBJECTIVES

Our purpose was to investigate whether with-no-K[Lys] kinase (WNK) 1 and WNK4 genetic polymorphisms are associated with both hypertension and diuretics response.

DESIGN AND METHODS

Two WNK1 and one WNK4 polymorphisms were detected in two independent populations (n = 1592 and 602) for association with hypertension, and in two clinical trials of hydrochlorothiazide treatment (n = 542 and 274) for association with diuretics response.

RESULTS

Two polymorphisms were found to be associated with hypertension risk with odds ratio of 1.55 for WNK1 rs1468326 (P<0.001) and 1.88 for WNK4 rs9916754 (P<0.001) in the first population, and 1.54 for WKN1 rs1468326, and 1.82 for WNK4 rs9916754 in the second population. However, two clinical trials found no relationship between these WNK polymorphisms and systolic/diastolic blood pressure responses to 4 or 8 weeks treatment of hydrochlorothiazide.

CONCLUSION

Our findings suggest that hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.

摘要

目的

我们旨在探究丝氨酸/苏氨酸激酶无丝氨酸/苏氨酸激酶 1（WNK1）和 WNK4 基因多态性是否与高血压和利尿剂反应均相关。

设计和方法

在两个独立人群（n=1592 和 602）中检测了两个 WNK1 多态性和一个 WNK4 多态性，以研究其与高血压的相关性，在氢氯噻嗪治疗的两项临床试验（n=542 和 274）中检测了其与利尿剂反应的相关性。

结果

在第一个人群中，两个多态性与高血压风险相关，WNK1 rs1468326 的比值比为 1.55（P<0.001），WNK4 rs9916754 的比值比为 1.88（P<0.001），在第二个人群中，WNK1 rs1468326 的比值比为 1.54，WNK4 rs9916754 的比值比为 1.82。然而，两项临床试验均未发现这些 WNK 多态性与氢氯噻嗪治疗 4 或 8 周后收缩压/舒张压反应之间存在关系。