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(Circulation. 1999;99:340-343.)
© 1999 American Heart Association, Inc.

Brief Rapid Communication

Prospective Evaluation of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of Stroke

Robert Y.L. Zee, BDS, PhD; Paul M. Ridker, MD, MPH; Meir J. Stampfer, MD, DrPH; Charles H. Hennekens, MD, DrPH; Klaus Lindpaintner, MD

From the Cardiovascular Division (R.Y.L.Z., P.M.R., K.L.), the Division of Preventive Medicine (P.M.R., C.H.H.), and the Channing Laboratory (M.J.S.), Department of Medicine, Brigham and Women's Hospital; the Department of Cardiology, Children's Hospital (K.L.); the Department of Ambulatory Care and Prevention, Harvard Medical School (C.H.H.); and the Departments of Epidemiology (M.J.S., C.H.H.) and Nutrition (M.J.S.), Harvard School of Public Health, Boston, Mass; the Pharmaceuticals Division of F. Hoffmann–La Roche (K.L.), Basel, Switzerland; and the Max Delbrück Center for Molecular Medicine (K.L.), Berlin, Germany.

Correspondence to Robert Y.L. Zee, BDS, PhD, Cardiovascular Division, Thorn 1203, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail rylz{at}calvin.bwh.harvard.edu

Background—The D/I polymorphism of the ACE gene has been studied in relation to a variety of cardiovascular disorders, including stroke. A number of small studies have been conducted, with inconsistent results. We investigated the association between ACE genotype and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians' Health Study.

Methods and Results—In the Physicians' Health Study, 348 subjects who had been apparently healthy at enrollment suffered a stroke during 12 years of follow-up, as determined from medical records and autopsy. A total of 348 cases were matched by age, time of randomization, and smoking habit to an equal number of controls (who had remained free of stroke). The D/I polymorphism was determined by polymerase chain reaction. Data were analyzed for the entire nested case-control sample, and also among a subgroup without a history of hypertension or diabetes mellitus, considered to be at low conventional risk (207 cases and 280 controls). All observed genotype frequencies were in Hardy-Weinberg equilibrium. The relative risk associated with the D allele was 1.11 (95% CI, 0.90 to 1.37; P=0.35), assuming an additive model in the matched analysis. Additional analyses assuming dominant or recessive effects of the D allele, as well as the analysis after stratification for low-risk status, showed no material as a statistically significant association.

Conclusions—The results of this large, prospective study indicate that the ACE D/I gene polymorphism is not associated with subsequent risk of stroke.

Key Words: angiotensin • enzymes • stroke • genetics

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