口服避孕药及血管紧张素转化酶基因多态性与女性脑卒中发病风险的关系

目的 评价口服避孕药(OC)暴露和血管紧张素转化酶(ACE)基因多态性及其联合作用对女性脑卒中发病风险的影响.方法 在前瞻性队列研究的基础上采用病例对照研究的方法,按照年龄(±3岁)和地区为每例女性脑卒中匹配一名同医院同期住院对照和一名邻里健康对照.采用普通PCR(ACE I/D)和实时荧光定量PCR (TagMan)(A-240T)方法进行基因型检测.结果 (1)妇女患脑卒中的风险随OC累积使用时间的增加而增加(P＜0.0001);(2) I/D位点的ID/DD基因型显著增加出血型脑卒中发病风险;(3)OC和ACE基因的联合作用增加出血型脑卒中的风险;(4)多因素logistic回归分析发现,OC和ID/DD基因型是出血型脑卒中的重要危险因素.结论 OC和ACE基因遗传易感性及其联合作用可能升高出血型脑卒中的发病风险.

Study on the association of oral contraceptives, angiotensin-converting enzyme gene polymorphisms and risk of stroke in women

Objective To evaluate the associations of oral contraceptives (OC) exposure,angiotensin-converting enzyme(ACE) gene polymorphism and their joint actions with the risk of stroke in Chinese women.Methods A case-control study,based on a set cohort,was carried out.Incident cases of stroke identified between July 1 1997 and June 30 2009 were enrolled.One hospital control and healthy community control were matched on region and age ( ± 3 years).A total of 453women with stroke and 919 controls were recruited.I/D genepolymorphism was detected by polymerase chain reaction (PCR) and amplification fragment length polymorphism (AFLP),A-240T polymorphism were detected by TagMan.Results ( 1 ) The risk of stroke gradually increased with the cumulative time of OC being used in women (P＜0.0001).Compared with non-users,the risk of stroke significantly increased among those with cumulative time of using OC longer than 20 years (adjusted OR was 2.07,with 95％ CI as 1.30-3.29).(2) ID/DD genotype of I/D locus indicated significantly an increased risk of hemorrhagic stroke (adjusted OR,2.37; 95％CI,1.46-3.84).(3)Women with ID/DD genotype of I/D locus or with TA/TT genotype of A-240T locus and using OC could significantly increase the risk of hemorrhagic stroke (adjusted OR was 4.59; with 95％ CI as 2.21-9.51 and OR was 2.50; with 95％CI as 1.42-4.38).(4) Data from multivariate analyses showed that both OC and ID/DD genotypes were important risk factors for hemorrhagic stroke.Conclusion ID/DD and TA/TT genotypes of ACE gene,OC and their joint action might increase the risk of stroke,especially on hemorrhagic stroke in Chinese women.