Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma.

BACKGROUND AND PURPOSE

A deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme gene has been associated with myocardial infarction. Its relations to both stroke and atheroma remain uncertain. We examined its role as a risk factor in patients with cerebrovascular disease and its relation to carotid atheroma.

METHODS

One hundred one patients with symptomatic carotid artery territory cerebral ischemia were compared with 137 age-matched control subjects. In the patient group, carotid atheroma was assessed by measurement of degree of carotid stenosis and intima-media thickness with high-resolution duplex ultrasound. The D/I polymorphism was examined using the polymerase chain reaction.

RESULTS

D:I allele frequency was 0.59:0.41 in case subjects and 0.48:0.52 in control subjects (P = .01). The DD genotype was more common in patients with cerebrovascular disease compared with control subjects (36/101 versus 30/137, P = .02). The DD genotype conferred a relative risk of any type of cerebrovascular disease of 1.98 (95% confidence interval [CI], 1.11 to 3.51; P = .02). However, this was largely due to a strong association in the 18 patients with lacunar stroke, in whom the D:I ratio was 0.75:0.25 (P = .0097 versus control subjects). The odds ratio for lacunar stroke associated with the DD genotype was 5.6 (95% CI, 2.0 to 15.7) and was still significant at 4.40 (95% CI, 1.45 to 12.6; P < .009) after controlling for other risk factors. There was no significant association between angiotensin-converting enzyme genotype and cerebrovascular disease due to large-vessel stenosis. There was no association between genotype and age, sex, smoking history, diabetes, or cholesterol level.

CONCLUSIONS

The deletion polymorphism in the angiotensin-converting enzyme gene is a new independent risk factor for lacunar stroke but is not a risk factor for stroke associated with carotid stenosis.