血管紧张素转换酶和醛固酮合成酶基因多态性与氢氯噻嗪降压疗效的关系

Association of polymorphisms in ACE and CYP11B2 genes with antihypertensive effects of hydrochlorothiazide

目的研究血管紧张素转换酶(ACE)基因I/D多态性和醛固酮合成酶(CYP11B2)基因-344T/C多态性与氢氯噻嗪降压疗效的关系。方法829例高血压病(EH)患者同时服用氢氯噻嗪12·5mg(1次/d),6周后资料完整的785例患者按不同ACE基因型和CYP11B2基因型分组,比较不同基因型和不同基因型组合间血压下降值有无差别。结果服用氢氯噻嗪6周后,ACE基因II、ID、DD型患者收缩压分别下降(5·1±14·8)mmHg(1mmHg=0·133kPa)、(4·8±16·3)mmHg和(9·4±15·7)mmHg,DD型患者下降值大于II、ID型患者,组间比较差异有统计学意义(P<0·00);CYP11B2基因TT、TC、CC型患者收缩压下降值分别为(5·8±16·2)mmHg、(5·5±14·9)mmHg和(7·6±16·1)mmHg,组间比较差异无统计学意义。DD+CC基因型患者收缩压下降值为(10·6±12·3)mmHg,高于其他基因型组合患者,但差异无统计学意义(P>0·05)。多因素分析结果表明DD基因型和治疗前醛固酮浓度是影响患者坐位收缩压下降的主要因素。结论ACE基因的DD型与氢氯噻嗪的降压疗效相关,CYP11B2基因CC型、DD+CC型患者对氢氯噻嗪的降压反应可能优于其他基因组合患者。

Objective To determine whether the blood pressure （BP） response to hydrochlorothiazide （HCTZ） was associated with the angiotensin converting-enzyme （ACE） I/D and aldosterone synthase （CYP11B2） -344T/C polymorphisms. Methods The BP response to HCTZ 12. 5 mg once daily for 6 weeks was assessed in 829 subjects with mild or moderate essential hypertension, and compared across the ACE and CYP11B2 genotypes. Results Of the 829 enrolled subjects, 785 completed the study. The systolic BP response differed according to the ACE （ DD 9.4 ± 15.7 mm Hg, ID 4. 8 ± 16. 3 mm Hg, and II 5.1 ± 14. 8 mm Hg, P 〈 0. 01 ）, but not the CYP11B2 genotype （P 〉0. 05）. Subjects with the combination of ACE DD and CYP11 B2 CC genotypes tended to have a more pronounced systolic BP reduction than the other genotypic combinations of these 2 genes. Multiple linear regression analyses showed that the ACE DD genotype and serum aldosterone concentration at baseline were associated with the systolic BP reduction after treatment. None of the genetic associations with changes in diastolic BP or mean arterial pressure reached statistical significance （ P 〉 0. 05 ）. Conclusions The present study suggested that the ACE DD genotype was associated with the systolic BP response to HCTZ, and that the subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better BP response to HCTZ than the other genotypic combinations of these 2 genes.