(Stroke. 1995;26:1329-1333.)
© 1995 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme Gene Deletion Polymorphism
A New Risk Factor for Lacunar Stroke but not Carotid Atheroma
From the University Department of Neurology, King's College School of Medicine and Dentistry (H.S.M.), and the Divisions of Clinical Neuroscience (H.S.M., M.M.B.), Medical Genetics (J.B., S.J., N.D.C.), Clinical Chemistry (R.L.), and Public Health Sciences (J.M.B.), St George's Hospital Medical School, London, UK.
Correspondence to Dr Hugh Markus, University Department of Neurology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
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.
Key Words: angiotensin-converting enzymes • carotid artery diseases • genetics • ultrasonics
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