Androgen Receptor CAG repeat is Associated with Fat Free Mass in Men but not in Women

Abstract

0713 PURPOSE: The human androgen receptor (AR) gene contains a polymorphic CAG repeat in the coding region of exon 1. A variable number of CAG repeats encodes for a variable number of glutamine residues in the AR protein and is inversely associated with transcriptional activity of the AR, which modulates the genomic effects of testosterone. Given the importance of androgens to muscle mass, the importance of the CAG repeat to AR function, and the known heritability of muscle mass, we hypothesized that individuals with greater numbers of AR gene CAG repeats would exhibit lower levels of total fat free mass (FFM) compared to individuals with fewer CAG repeats. METHODS: 202 Caucasian volunteers (112 men and 90 women) aged 19–90 years were typed to determine the number of AR CAG repeats using standard polymerase chain reaction techniques. Subjects were grouped by allele length of <287 bp or ≤Ý287 bp. Whole-body soft tissue composition was measured by dual-energy X-ray absorptiometry (DXA). Dependent variables were analyzed using analysis of covariance. RESULTS: No significant differences were observed for height, weight, BMI, or physical activity between the two groups. Sample size was as follows: men <287 bp = 51, ≤Ý287 bp = 61, women <287 bp = 52, ≤Ý287 bp = 38. Contrary to our hypothesis, males with the longer CAG repeat exhibited significantly greater total FFM (53.8 ± 1.1 vs. 57.2 ± 1.1 kg, P < 0.05) and relative total FFM (normalized to height; 17.8 ± 0.3 vs. 18.7 ± .3 kg/m2, P < 0.05) compared to the shorter CAG group. There were no significant differences between groups for women. CONCLUSION: The androgen receptor exon 1 CAG repeat polymorphism is associated with fat free mass in men but not in women. Supported by NIA intramural funds, AG21500, and AG22791.