The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

Aims/hypothesis. The relationship of androgens to the metabolic syndrome has not been resolved. The polymorphic number of CAG repeats within the androgen receptor gene is inversely associated with the transcriptional activity of target genes. This polymorphism might thus influence testosterone effects on body fat content and serum concentrations of leptin and insulin. The direct and indirect role of androgens within the metabolic syndrome should become clearer if this genetically determined effector is taken into account. Methods. The hypothesis was investigated in a cross-sectional study involving 106 healthy 20-50 year old males. Results. Multiple regression models showed a positive independent correlation of the CAG repeat number with body fat content, leptin and insulin (partial r = 0.39, 0.36 and 0.28, p < 0.001, p < 0.001 and p = 0.006, respectively). Factor analysis yielded a five-dimensional model: two dimensions were influenced by the androgen receptor polymorphism, namely body composition which consisted of leptin, body fat mass, insulin, the number of CAG repeats (positive loadings) and physical activity (negative loading), and lipid profile which comprised low density lipoprotein cholesterol, cigarette smoking, triglycerides (positive loadings) as well as high density lipoprotein cholesterol and number of CAG repeats (negative loadings). Conclusions/interpretation. A low number of CAG repeats were independently associated with protective parameters (low body fat mass and plasma insulin) as well as with adverse parameters (low high density lipoprotein cholesterol concentrations). This suggests that the pivotal role of this polymorphism in modulating androgen effects on cardiovascular risk factors is of a complex nature and implies that its clinical impact, similar to that of androgens, is dependent on exogenous cofactors.