Androgen receptor GGC repeat might be more involved than CAG repeat in the regulation of the metabolic profile in men.

Abstract

The influence of androgen receptor (AR) GGC repeat polymorphism on the metabolic profile of men has been much less studied than the one of CAG tract polymorphism. Therefore, in this study, we looked for the association of GGC and CAG tract with cardiovascular risk factors in men. Ninety-eight men followed by our andrological unit were retrospectively reviewed. Clinical and biochemical parameters on cardiovascular risk were considered. AR CAG and GGC polymorphisms were studied. GGC triplets were found to be positively and significantly correlated with several cardiovascular risk factors. On the other hand, inverse and significant correlations of CAG triplets were found with insulin and HOMA. As expected, age was positively correlated with cardiovascular risk, whereas total testosterone was inversely correlated with metabolic profile. Estradiol was not found to be correlated with any of the metabolic parameters. In the total sample, multivariate linear regression analysis confirms the positive and independent association of GGC triplets with glycemia, glycated hemoglobin, total cholesterol, triglycerides and homeostasis model assessment of insulin resistance (HOMA), whereas CAG repeat length is negatively associated with insulin and HOMA. Such associations are also substantially confirmed in non-diabetic subjects, whereas in diabetic patients only the GGC tract seems to be involved in the metabolic profile regulation. Our work shows a relevant role for GGC repeat tract in conditioning male cardiovascular risk, thus rendering necessary a deeper analysis on the role of GGC polymorphism both from the molecular and the clinical point of view.