CYP11B2基因多态性对不同性别肾素-血管紧张素-醛固酮系统活性及降压疗效的影响  

Effect of CYP11B2 gene -- 344T/C polymorphism on renin-angiotensin-aldosterone system activity and blood pressure response to hydrochlorothiazide

作　　者：李云[1] 杨鹏[1] 吴寿岭[1] 袁聚祥[1] 武英[1] 赵丹丹[1] 徐胜[2] 赵丽萍[2] 孙满江[2] 褚立明[1] 鲁大双[1] 

机构地区：[1]河北联合大学公共卫生学院,河北省唐山市063007 [2]唐山市人民医院

出　　处：《中华医学遗传学杂志》2012年第1期68-71,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81000110）

摘　　要：目的探讨CYP11B2基因-344T／C多态性对于不同性别高血压病患者肾素-血管紧张素-醛固酮系统（renin-angiotensin-aldosterone system，RAAS）活性及降压疗效的影响。方法共选择了829例轻、中度高血压病患者，所有患者先经过2周的安慰剂清洗期，随后给予6周氢氯噻嗪口服12．5mg／d。分别在清洗期末和6周氢氯噻嗪治疗期末测定血压水平和各种生化指标，分析CYP11B2基因-344T／C多态性对不同性别高血压患者RAAS活性及降压疗效的影响。结果共有776例患者完成研究，其中17．5％的患者血压达到正常水平。在男性中，CYP11B2基因CC基因型患者血清醛固酮水平显著高于TT、TC基因型，差异有统计学意义（Pd0．05）；CC基因型男性服用氢氯噻嗪后有血压下降幅度低于其他基因型男性、醛固酮升高幅度高于其他基因型男性的趋势，但差异均无统计学意义（P〉0．05）。在女性中，CYP11B2基因-344T／c多态性与血清醛固酮水平无关，服用氢氯噻嗪后CC基因型女性有血压下降幅度高于其他基因型女性、醛固酮升高幅度低于其他基因型女性的趋势，但差异均无统计学意义（P〉0．05）。结论男性高血压患者CC基因型与血清醛固酮水平较高相关，服用氢氯噻嗪后血清醛固酮水平高增高及血压水平低下降；女性高血压患者CC基因型与血清醛固酮水平无明显相关，服用氢氯噻嗪后表现也与男性相反。Objective To evaluate the effect of CYP11B2 gene --344T/C polymorphism on renin- angiotensin-aldosterone system （RAAS） activity and blood pressure in response to hydrochlorothiazide （HCTZ） treatment in Han Chinese patients with essential hypertension. Methods Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period （baseline） and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYPllB2 -- 344T/C polymorphism and gender. Results A total of 776 patients completed the study. 17. 50% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYPllB2 --344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. Conclusion In males, the --344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.

关 键 词：高血压病 CYP11B2基因 遗传多态性 利尿剂 性别 

分 类 号：R544.1[医药卫生—心血管疾病]