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

Although genetic factors may be important in the pathogenesis of ischemic stroke (IS), little is known on the potential role of genes in most cases of hemorrhagic stroke (HS). Preliminary data showed that the TT genotype of the alpha(1)-antichymotrypsin (ACT) gene polymorphism was associated with HS, although it remained unsettled whether prevalence of this polymorphism might differ between hypertensive and normotensive HS.

Ninety-nine patients with HS, 182 patients with IS (symptomatic control subjects), and 80 asymptomatic control subjects were genotyped for the ACT polymorphism using polymerase chain reaction amplification. Chronic hypertension was recorded in 66 patients with HS.

The ACT-TT genotype was more prevalent in patients than in asymptomatic 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 restricted 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.

These findings confirm in a larger series of patients the association between the ACT-TT genotype and HS. This polymorphism is more prevalent in normotensive bleedings. Pathological studies will be required to establish whether the ACT-TT genotype facilitates proteolytic rupture of vessels that harbor amyloidotic changes or another form of nonhypertensive cerebral angiopathy.