Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men.
OBJECTIVE
The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings.


METHODS
677 men (25-45 years) were recruited in a cross-sectional, population-based sibling pair study.


METHODS
Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling.


RESULTS
Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats.


CONCLUSIONS
Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also affect muscle mass or function.
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium ; Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
Hélène
H
De Naeyer
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Veerle
V
Bogaert
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Annelies
A
De Spaey
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Greet
G
Roef
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Sara
S
Vandewalle
Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
Wim
W
Derave
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Youri
Y
Taes
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium ; Unit for Osteoporosis and Metabolic bone diseases, Ghent University Hospital, Ghent, Belgium.
Jean-Marc
JM
Kaufman
D000328:Adult; D001823:Body Composition; D003430:Cross-Sectional Studies; D056726:Genetic Association Studies; D018737:Hand Strength; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology*; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics*; D035781:Siblings; D013739:Testosterone / Q000097:blood*
D011944:Receptors, Androgen; D013739:Testosterone