alpha(1)-antichymotrypsin polymorphism - A risk factor for hemorrhagic stroke in normotensive subjects

Background and Purpose-Although genetic factors may be important in the pat hogenesis of ischemic stroke (IS), little is known on the potential role of genes in most cases of hemorrhagic stroke (HS). Preliminary data showed th at the TT genotype of the alpha (1)-antichymotrypsin (ACT) gene polymorphis m was associated with HS, although it remained unsettled whether prevalence of this polymorphism might differ between hypertensive and normotensive HS . Methods-Ninety-nine patients with HS, 182 patients with IS (symptomatic con trol Subjects), and 80 asymptomatic control subjects were genotyped for the ACT polymorphism using polymerase chain reaction amplification. Chronic hy pertension was recorded in 66 patients with HS. Results-The ACT-TT genotype was more prevalent in patients than in asymptom atic or symptomatic control subjects: 26%, 15%, and 16%, respectively. The ACT-TT genotype was obtained in 33% of HS who lacked arterial hypertension (P <0.05). After adjustment for age, gender, and vascular risk factors, the ACT-TT genotype remained independently associated with HS (OR 2.80, 95% CI 1.19 to 6.58, compared with asymptomatic control Subjects; OR 1.79, 95% CI 0.95 to 3.40, compared with symptomatic control subjects). In analyses res tricted to HS in normotensive patients, the ORs were 3.10 (95% CI 1.10 to 8 .68) and 2.53 (95% CI 1.04 to 6.18), respectively. Conclusions-These findings confirm in a larger series of patients the assoc iation between the ACT-TT genotype and HS. This polymorphism is more preval ent in normotensive bleedings. Pathological studies will be required to est ablish whether the ACT-TT genotype facilitates proteolytic rupture of vesse ls that harbor amyloidotic changes or another form of nonhypertensive cereb ral angiopathy.