Contributions by the CAG-repeat Polymorphism of the Androgen Receptor Gene and Circulating Androgens to Muscle Size. Odense Androgen Study - A Population-based Study of 20-29 Year-old Danish Men | Torben Leo Nielsen, Claus Hagen, Kristian Wraae, Rasmus Larsen, Egil Haug, Kim Brixen, Marianne Andersen
| | Abstract | Context: The number of CAG-repeats within the CAG-repeat polymorphism of the androgen receptor gene is inversely correlated with the transcriptional activity of the androgen receptor.
Objective: To study the effect of the CAG-repeat number and circulating androgens on muscle size, to examine the CAG-repeat number in relation to body fat mass and circulating androgens, and to identify the best hormonal marker of low muscle size amongst total testosterone, bioavailable testosterone, and dihydrotestosterone.
Design, Setting, and Participants: Population-based study of 783 Danish men aged 20-29 years, who matched the background population as regards body mass index, chronic disease, medication, physical activity, smoking, and sociodemographic parameters. Genotyping was performed in 767 men, whole body DXA in 783 men, and MRI in 406 consecutively included men.
Main Outcome Measures: Six continuous outcomes (thigh and axial muscle area, lower extremity, upper extremity, and trunk lean body mass, and total body fat mass) and five binary outcomes of low muscle size defined as men with muscle size below the lower 10 percentile of each continuous outcome of muscle size.
Results: The CAG-repeat number correlated inversely with thigh and axial muscle area and with lower and upper extremity lean body mass. Except for upper extremity lean body mass, these findings remained significant in multivariate analyses controlling for circulating androgens, physical activity, smoking, alcohol intake, chronic disease, and age. The CAG-repeat number correlated positively with total body fat mass adjusted for weight, but not with the concentration of any of the circulating androgens. Total testosterone and dihydrotestosterone correlated positively with all outcomes of muscle size. The prevalence of low muscle size increased exponentially with decreasing androgen levels and was tripled at total testosterone levels <12.5 nmol/l (the lower reference limit for total testosterone in 615 healthy, non-obese men of this cohort).
Conclusion: The CAG-repeat polymorphism affects body composition in young men, independently of circulating androgens and the covariates: Fewer repeats are related with increased muscle size and reduced total body fat mass. The polymorphism does not affect androgen levels. Both total testosterone and dihydrotestosterone correlate with muscle size in a linear concentration-response relationship. Total testosterone is the best biomarker of low muscle size in young men.
Sources of Support: World Anti-Doping Agency; Novo Nordic; Pfizer; The Danish Ministry of Culture; University of Southern Denmark; Odense University Hospital | | Keywords | Genetics, Testosterone, Body composition | | Type | Conference paper [Abstract] | | Conference | Proceedings of the Endocrine Society's 89th Annual Meeting | | Year | 2007 | | BibTeX data | [bibtex] | | IMM Group(s) | Image Analysis & Computer Graphics |
|