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

Abstract

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 Ն21 (or Ն22) and risk of CVD, myocardial infarctions or ischemic stroke. [CAG] repeats in the amino-terminal domain, has been associated with higher testosterone levels in women, 1 as well as lower HDL levels, 2 impaired endothelial vasodilation, 2 and increased odds of coronary heart disease 3 in men. However, to the best of our knowledge, associations between AR genetic variation and cardiovascular disease (CVD) have not been evaluated in women. We examined 6 haplotype-tagging single nucleotide polymorphisms (htSNPs) and the CAG repeat microsatellite in exon 1 in a nested case-control study within the Women's Health Study (WHS). Conclusions-No Materials and Methods Study DesignA nested case-control study was performed within the WHS, a randomized trial of aspirin and vitamin E among 39 876 female health professionals. 4 Before randomization, 28 345 participants provided an EDTA-anticoagulated blood sample. Participants were free of known CVD and cancer at study entry. Yearly questionnaires ascertained newly developed CVD, and medical records were used to confirm events. 4 Before February 2004, 855 cases of first myocardial infarction or ischemic stroke occurred, with 458 meeting all our inclusion criteria (white postmenopausal women with data on smoking and hormone therapy). For 158, bloods were unavailable, leaving 300 cases for the present analysis. Compared to cases without blood, cases with blood available had similar BMI and hormone therapy use rates, but were slightly younger and less likely to smoke. For each case, a WHS control, who met these criteria but remained free from CVD until the case event, was matched by age, smoking status and use of postmenopausal hormone therapy.The study was approved by the Brigham and Women's Hospital Institutional Review Board for Human Subjects...

Androgen receptor gene and sex-specific Alzheimer's disease

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Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences

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Lack of Influence of the Androgen Receptor Gene CAG-Repeat Polymorphism on Clinical and Electrocardiographic Manifestations of the Brugada Syndrome in Man

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