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Published Online
on March 6, 2008

Stroke. 2008
Published online before print March 6, 2008, doi: 10.1161/STROKEAHA.107.508218
A more recent version of this article appeared on May 1, 2008
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Submitted on October 24, 2007
Accepted on October 31, 2007

Genetic Variation of the Androgen Receptor and Risk of Myocardial Infarction and Ischemic Stroke in Women

Kathryn M. Rexrode MD, MPH*; Paul M. Ridker MD, MPH; Hillary H. Hegener BS; Julie E. Buring ScD; JoAnn E. Manson MD, DrPH; and Robert Y.L. Zee PhD

From the Division of Preventive Medicine (K.M.R., P.M.R., H.H.H., J.E.B., J.E.M., R.Y.L.Z.), and the Center for Cardiovascular Disease Prevention (P.M.R., H.H.H., R.Y.L.Z.), Brigham and Women's Hospital, Harvard Medical Schoo, Boston, Mass; the Department of Epidemiology (J.E.B., J.E.M.), Harvard School of Public Health, Boston, Mass; and the Department of Ambulatory Care and Prevention (J.E.B.), Harvard Medical School, Boston, Mass.

* To whom correspondence should be addressed. E-mail: krexrode{at}partners.org.

Background and Purpose—Androgen receptors (AR) are expressed in endothelial cells and vascular smooth-muscle cells. Some studies suggest an association between AR gene variation and risk of cardiovascular disease (CVD) in men; however, the relationship has not been examined in women.

Methods—Six haplotype block-tagging single nucleotide polymorphisms (rs962458, rs6152, rs1204038, rs2361634, rs1337080, rs1337082), as well as the cysteine, adenine, guanine (CAG) microsatellite in exon 1, of the AR gene were evaluated among 300 white postmenopausal women who developed CVD (158 myocardial infarctions and 142 ischemic strokes) and an equal number of matched controls within the Women's Health Study.

Results—Genotype distributions were similar between cases and controls, and genotypes were not significantly related to risk of CVD, myocardial infarctions or ischemic stroke in conditional logistic regression models. Seven common haplotypes were observed, but distributions did not differ between cases and controls nor were significant associations observed in logistic regression analysis. The median CAG repeat length was 21. In conditional logistic regression, there was no association between the number of alleles with CAG repeat length ≥21 (or ≥22) and risk of CVD, myocardial infarctions or ischemic stroke.

Conclusions—No association between AR genetic variation, as measured by haplotype-tagging single nucleotide polymorphisms and CAG repeat number, and risk of CVD was observed in women.


Key words: cardiac emboli • cerebral infarct • genetics • women & minorities • androgens