Androgen receptor gene CAG(n) repeat polymorphism and coronary artery disease (CAD) in women
Maria Alevizaki1,2, Katerina Saltiki1,2, Adriana Cimponeriu1, Maria Garofalaki1, Emily Mantzou1 & Kimon Stamatelopoulos1
Objective: Androgen may be detrimental for vascular health in women. Sensitivity to androgen is influenced by the CAG repeat length of the androgen receptor (AR) gene. We investigated possible associations between the CAG repeat polymorphism with the severity of CAD in women undergoing coronary angiography.
Methods: We examined 131 postmenopausal women (4588 years). CAD severity was assessed by the number of coronary vessels with >50% stenosis. History of angina, number of myocardial infarctions (MI), hormonal and biochemical parameters were recorded. The number of CAG repeats ranged between 13 and 28. The mean lowest quartile corresponded to 19 and the highest to 22 repeats.
Results: Angina was more frequent in those carrying ≤19 repeats compared to ≥22 repeats (P=0.037, Fishers exact). A higher percentage of women carrying ≤19 ARgene CAG repeats had 1 and 2 MIs (28.6 and 10.7%) compared to women with >19 repeats (18.2 and 1.45% respectively, P=0.019). Carriers of ≤19 repeats in their shorter allele had severe disease (≥2 vessels affected) more frequently compared to those carrying ≥22 repeats (39.2% vs 9.5%, P=0.009 Fisher exact). Cholesterol and LDL levels were negatively correlated with the number of repeats of the shorter allele (r=−0.203, P=0.029 and r=−0.196, P=0.039 respectively). Antilipid drug therapy was less frequent among carriers of longer repeats in both alleles (P=0.025). Mean SHBG levels were lower in women carrying the shorter CAG repeat number (<22 vs ≥22 repeats: 41±17 vs 53.8±30 nmol/l, P=0.03).
Conclusions: Shorter polyglutamine stretch in the androgen receptor gene, indicative of increased androgen action, is associated with more severe CAD in postmenopausal women undergoing coronary angiography, both concerning clinical manifestations and angiographic findings. This effect may be mediated by adverse lipid profile or SHBG levels. This association may support the adverse cardiovascular effect of life-long androgenic exposure in this highly selected group of women.