The importance of the (TAAAA)n alleles at the SHBG gene promoter for the severity of coronary artery disease in postmenopausal women

Abstract

Androgen may be detrimental in the development of coronary artery disease (CAD) in women. We investigated possible associations between the (TAAAA)n polymorphism of sex hormone-binding globulin (SHBG) gene promoter, which influences transcriptional efficiency of the SHBG gene and the severity of CAD in women. In this prospective clinical study, 146 postmenopausal women (46-88 y) undergoing coronary angiography were studied. CAD severity, history of angina and myocardial infarction, and reproductive history were recorded and hormonal parameters measured. According to the number of SHBG gene promoter repeat polymorphisms, participants were classified into short (seven or fewer), medium length (eight), and long repeat (nine or more) allele groups. Significant CAD was more prevalent in the long repeat allele carrier group: 65% of the participants with three vessels with severe stenosis belonged to the long repeat allele group, whereas only 37% of participants with mild CAD belonged to this group (P=0.01). A history of angina and prevalence of hyperlipidemia was more frequent in the long repeat allele group (P<0.05). Calculated free testosterone levels were higher in the long repeat allele groups (P<0.05), whereas SHBG levels tended to be lower (P=0.06). SHBG levels correlated inversely with body mass index and waist circumference (P<0.05). Longer (TAAAA)n repeats in the SHBG gene promoter are associated with more severe CAD in women undergoing coronary angiography, a finding not previously reported. This association may reflect the lifelong tissue exposure to higher free androgens and supports the adverse cardiovascular effect of androgenic exposure in this highly selected group of women.