Objective: Androgen may be detrimental in the development of cardiovascular disease 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 thus the tissue androgen availability and early markers of atherosclerosis in apparently healthy women.
Design and methods: In this prospective clinical study, 153 consecutive women (mean age 43.9±9 years, 66 of whom postmenopausal, without known diabetes, hypertension, cardiovascular disease), visiting our internal medicine outpatients were examined for unrecognised features of the metabolic syndrome. Endothelium dependent vasodilatation (FMD), an early marker of atherosclerosis, and intima media thickness (IMT) of the common carotid artery were recorded. According to the number of SHBG gene promoter repeats patients were classified as short (≤7), medium (=8) and long repeat (≥9) allele groups.
Results: There was a significant negative correlation between FMD and the length of the two polymorphic alleles that each woman carried (P=0.032 and P=0.01, for the shorter and longer allele, respectively). IMT of the common carotid had a positive correlation with the length of the shorter allele (P=0.015). Women carriers of two long alleles had increased IMT (P=0.037, Anova). These associations were independent of BMI, abdominal obesity and HOMA insulin resistance index (step multivariate analysis, P=0.001). Mean SHBG levels tended to be higher in women carrying the longer alleles (P=0.06). Finally in the subgroup of premenopausal women there was a significant positive correlation between SHBG levels and FMD (P=0.037).
Conclusions: Longer (TAAAA)n repeats in the SHBG gene promoter are associated with impaired FMD and increased carotid artery IMT, both of which are early markers of atherosclerosis. This association may reflect the life-long tissue exposure to higher free androgens and indirectly supports the view that androgenic exposure may have adverse cardiovascular effects in women.