Wu Sheng-Nan, Zhang Yi, Gardner Charles O, Chen Qi, Li Yan, Wang Gu-Liang, Gao Ping-Jin, Zhu Ding-Liang
Shanghai Key Laboratory of Vascular Biology at Ruijin Hospital and Shanghai Institute of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Ann Hum Genet. 2007 Jul;71(Pt 4):519-25. doi: 10.1111/j.1469-1809.2007.00346.x. Epub 2007 Feb 5.
Evidence from animal models and human studies suggests that CYP2J2 plays a mechanistic role in the development of hypertension. The present study aims to investigate the potential genetic contribution of the CYP2J2 gene to the etiology of essential hypertension (EH) and individual blood pressure.
We selected eight polymorphisms in/or around the CYP2J2 gene and performed a case-control association study involving 841 Han Chinese subjects, including 415 unrelated hypertensives and 426 age-, gender- and area-matched normotensives.
Three functionally identified variants (CYP2J2 *2, *7 and CYP2J2 *8) and SNP rs11572182 represented rare polymorphisms in Han Chinese. However, the difference in rs1155002 genotype distribution between hypertensive and healthy subjects was close to significance (P = 0.06) in the whole sample. Interestingly, significant evidence for an association with rs1155002 was found in females when stratified by gender. In females, the TT homozygote of rs1155002 seems to be a risk factor for hypertension (p = 0.014). In addition, ANOVA analysis suggested TT carriers had significantly higher systolic blood pressure (p = 0.016). The genotype frequencies for rs10493270, rs1180273 and rs1324491 revealed no statistically significant differences. Likewise, four-marker haplotype frequencies showed no significant differences between cases and controls.
Our data provide strong evidence that the CYP2J2 gene is a susceptibility factor for essential hypertension, especially in females, and influences individual systolic blood pressure in the Chinese Han population.
来自动物模型和人体研究的证据表明，CYP2J2在高血压的发生发展中起机制性作用。本研究旨在探讨CYP2J2基因对原发性高血压（EH）病因及个体血压的潜在遗传贡献。
我们在CYP2J2基因内部及周围选择了8个多态性位点，并对841名汉族受试者进行了病例对照关联研究，其中包括415名无亲缘关系的高血压患者和426名年龄、性别及地区匹配的血压正常者。
三个功能明确的变异体（CYP2J2 *2、*7和CYP2J2 *8）以及单核苷酸多态性rs11572182在汉族人群中表现为罕见多态性。然而，在整个样本中，高血压患者与健康受试者之间rs1155002基因型分布的差异接近显著水平（P = 0.06）。有趣的是，按性别分层时，在女性中发现了与rs1155002关联的显著证据。在女性中，rs1155002的TT纯合子似乎是高血压的一个危险因素（p = 0.014）。此外，方差分析表明TT携带者的收缩压显著更高（p = 0.016）。rs10493270、rs1180273和rs1324491的基因型频率未显示出统计学上的显著差异。同样，四标记单倍型频率在病例组和对照组之间也没有显著差异。
我们的数据提供了有力证据，表明CYP2J2基因是原发性高血压的一个易感因素，尤其是在女性中，并影响中国汉族人群的个体收缩压。
