Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Am J Hypertens. 2010 Jan;23(1):70-7. doi: 10.1038/ajh.2009.190. Epub 2009 Oct 22.
Hypertension is a major risk factor for cardiovascular disease. Although genetic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals.
A total of 5,734 Japanese individuals from two independent populations were examined: subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
The chi(2)-test revealed that 10 polymorphisms were significantly (P < 0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A-->G polymorphism (rs645106) of SDK1 and the C-->G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the A-->G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition.
SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined.
高血压是心血管疾病的主要危险因素。尽管遗传研究表明，几种遗传变异会增加患高血压的风险，但导致这种疾病遗传易感性的基因仍有待确定。本研究旨在确定导致日本个体患高血压的遗传变异。
本研究共检查了来自两个独立人群的 5734 名日本个体：研究对象 A 组包括 2066 名高血压患者和 824 名对照者；研究对象 B 组包括 834 名高血压患者和 2010 名对照者。本研究中检查的 150 个多态性是通过使用 GeneChip Human Mapping 500K Array Set（Affymetrix）对心肌梗死和缺血性中风进行全基因组关联研究选择的。
卡方检验显示，10 个多态性与研究对象 A 中高血压的患病率显著相关（P <0.05）。为了验证这些关系，在研究对象 B 中检查了这些多态性。SDK1 的 A-->G 多态性（rs645106）和 RABGAP1L 的 C-->G 多态性（rs12078839）与研究对象 B 中的高血压显著相关。经过协变量调整的多变量逻辑回归分析以及逐步向前选择程序表明，SDK1 的 A-->G 多态性与研究对象 A 和 B 中的高血压均显著相关，G 等位基因可预防该疾病。
尽管未确定鉴定出的多态性的功能相关性，但 SDK1 可能是日本个体患高血压的易感基因。
