The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity

Genomic effects of T are exerted via the AR. The length of the polymorphic CAG repeat sequence in the AR gene is inversely correlated with the transcr iptional regulation of target genes by T. In 110 healthy men (20-50 yr), we investigated the interactions among this polymorphism, serum levels of sex hormones, cardiovascular risk factors, and flow-mediated and nitrate-induc ed vasodilatation of the brachial artery. The number of CAG repeat had no s ignificant correlations with serum concentrations of total or free T. Stepw ise multiple regression analysis revealed positive correlations of the numb er of CAG repeat with serum levels of high density lipoprotein cholesterol (partial r = 0.44; P < 0.001) and flow-mediated vasodilatation (partial r = 0.37; P < 0.001). The association of CAG repeat with high density lipoprot ein (HDL) cholesterol was independent of body fat content and serum levels of free T, which both had significant negative correlations with HDL, chole sterol. The association of CAG repeat with flow-mediated vasodilatation was independent of cigarette smoking and serum levels of free T and low densit y lipoprotein cholesterol, which also were correlated with flow-mediated va sodilatation. We conclude that a low number of CAG repeat in the AR gene im plies a greater chance for low levels of HDL cholesterol and reduced endoth elial response to ischemia, which are both important risk factors for coron ary heart disease.