This Article Full Text Full Text (PDF) All Versions of this Article: 37/7/1686    most recent 01.STR.0000226994.93914.6cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zee, R. Y.L. Articles by Ridker, P. M Search for Related Content PubMed PubMed Citation Articles by Zee, R. Y.L. Articles by Ridker, P. M Related Collections Epidemiology Genetics of cardiovascular disease

(Stroke. 2006;37:1686.)
© 2006 American Heart Association, Inc.

Original Contributions

Polymorphisms in the Advanced Glycosylation End Product–Specific Receptor Gene and Risk of Incident Myocardial Infarction or Ischemic Stroke

Robert Y.L. Zee, PhD; Jose R. Romero, PhD; Jessica L. Gould, BS; Dennis A. Ricupero, PhD Paul M Ridker, MD

From the Center for Cardiovascular Disease Prevention, the Donald W. Reynolds Center for Cardiovascular Research, the Leducq Center for Molecular and Genetic Epidemiology (R.Y.L.Z., J.L.G., P.M.R.), and the Division of Endocrinology, Diabetes, and Hypertension (J.R.R., D.A.R.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Dr Robert Y.L. Zee, Laboratory of Genetic and Molecular Epidemiology, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02215. E-mail rzee{at}rics.bwh.harvard.edu

Background and Purpose— Recent findings of an association between polymorphisms of advanced glycosylation end product–specific receptor (AGER) and risk of diabetic vasculopathy have generated great interest. However, to date, no genetic–epidemiological data are available on risk of atherothrombotic events among nondiabetic populations.

Methods— Using DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we evaluated 3 AGER genetic variants: –429T>C, –374T>A, and Gly82Ser, among 600 white individuals who subsequently developed atherothrombotic event (incident myocardial infarction or ischemic stroke) and among 600 age- and smoking-matched white individuals who remained free of reported vascular disease during follow-up (controls).

Results— Genotype distributions for the polymorphisms tested were in Hardy–Weinberg equilibrium. Haplotype-based conditional logistic regression, adjusting for other potential confounders, showed that haplotype C-T-Gly (myocardial infarction: odds ratio [OR], 0.60; 95% CI, 0.41 to 0.90; P=0.01) and haplotype T-A-Gly (ischemic stroke: OR, 0.63; 95% CI, 0.40 to 0.99; P=0.05), compared with the reference haplotype T-T-Gly, were associated with reduced risk of atherothrombosis. Prespecified analysis limited to those without baseline history of diabetes showed similar significant findings.

Conclusions— We found an association of specific AGER promoter gene haplotypes with reduced risk of incident myocardial infarction and ischemic stroke that was independent of the presence of diabetes.

Key Words: genetics • polymorphism • risk factors