Objective: Androgen may adversely affect vascular health in women. We investigated the associations between the androgen receptor gene (CAG)n repeat polymorphism, which affects androgen receptor transcriptional activity, and the severity of coronary artery disease (CAD) in women undergoing coronary angiography.
Methods: We examined 131 postmenopausal women (46-82 y). CAD severity was assessed by the number of vessels with greater than 50% stenosis. The history of angina, myocardial infarctions, and biochemical parameters were recorded. CAG repeats ranged between 13 and 24 in the shorter allele and 16 and 28 in the longer allele. The mean lowest quartile corresponded to 19, and the highest, to 22 repeats.
Results: Carriers of 19 repeats or less in their shorter allele had severe disease (≥2 vessels affected) and a history of angina more frequently than those carrying 22 or more (39.2% vs 9.5%, P = 0.009 and 80.8% vs 55%, P = 0.037, respectively, using the Fisher exact test). A higher percentage of women carrying 19 repeats or less had one and two myocardial infarctions (28.6% and 10.7%, respectively) compared with women with more than 19 repeats (18.2% and 1.45%, respectively, P = 0.019). Women homozygous for two longer alleles (≥22 repeats) had less severe CAD, significantly higher sex hormone-binding globulin levels, and less frequent antilipid drug therapy compared with those homozygous for shorter alleles (P < 0.05). Total cholesterol and low-density lipoprotein cholesterol levels were negatively correlated with the number of repeats in the shorter allele (P < 0.04).
Conclusions: Shorter polyglutamine stretch in the androgen receptor correlates with more severe CAD and worse predisposing factors in postmenopausal women undergoing coronary angiography. This association may support the adverse cardiovascular effect of lifelong androgenic exposure in this selected group of women.