血管紧张素转换酶2基因多态性与抗高血压药物降压反应的相关性研究

Association of Polymorphisms of Angiotensin-Converting Enzyme 2 Gene With Antihypertensive Effects of Captopril in Women

目的:探讨血管紧张素转换酶(ACE)2基因多态性与抗高血压药物降压治疗反应的相关性。方法:设计为社区基础的随机、双盲临床试验。入选3408例未治疗高血压患者,随机分配到双氢克尿噻组(891例)、阿替洛尔组(594例)、硝苯地平缓释剂组(947例)和卡托普利组(976例)单药治疗4周,比较治疗前、后血压。选择ACE2基因2个标签单核苷酸多态及ACE基因I/D多态,采用标准的PCR-RFLP技术进行基因分型,抽取部分测序验证。结果:ACE2rs2106809基因型与女性高血压患者卡托普利治疗后舒张压降压反应相关(P=0.003)。多元回归分析调整治疗前血压、年龄,体重指数,空腹血糖及ACEI/D多态后,携带ACE2rs2106809TT+CT基因型的女性高血压患者卡托普利治疗后舒张压下降较CC基因型携带者显著减少3.3mmHg(P=0.019)。协方差分析发现ACE2rs2106809CC和CT+TT基因型间舒张压降压反应差异卡托普利组显著大于其它药物组(P=0.009)。结论:ACE2T等位基因影响女性对卡托普利治疗的舒张压降压反应。

Objective ： Some polymorphisms in genes of renin-angiotensin system are associated with the blood pressure response to anti- hypertensive drugs. This study investigated the association of polymorphisms of ACE2 and ACE with blood pressure response to antihypertensive medications. Methods ：A total of 3,408 untreated hypertensive patients were randomized to Captopril, Atenolol, Hydrochlorottfiazide, or Nifedipine sustained release treatments for 4 weeks to determine the association of blood pressure response with polymorphisms of ACE2. Two single nucleotide polymorphisms of ACE2 and ACE I/D were genotyped by standard PCR restriction fragment length polymorphism analysis, and subsequently confirmed by randomly selected bidirectional sequencing. Results：Female hypertensive carriers of ACE2 rs2106809 T allele had 3.3 mmHg lower reduction in diastolic blood pressure response to captopril than did CC genotype female carriers after adjusting for pretreatment blood pressure, age, body mass index, and ACE I/D polyrnorphism（ P =0. 019） ,but this association was not found in men and in other antihypertensive drug treatment groups. No association was found between ACE DD genotype and blood pressure response to any antihypertensive drugs. The difference between CC and CT ＋ TT genotype groups was larger in captopril group than in group aggregated other drugs in women. Conclusion：ACE2 T allele can affect blood pressure responses to ACE inhibitors in women.