Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men

PLoS One. 2014 Jan 23;9(1):e86235. doi: 10.1371/journal.pone.0086235. eCollection 2014.


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.

Design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Composition
  • Cross-Sectional Studies
  • Genetic Association Studies
  • Hand Strength
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / anatomy & histology*
  • Polymorphism, Single Nucleotide*
  • Receptors, Androgen / genetics*
  • Siblings
  • Testosterone / blood*


  • Receptors, Androgen
  • Testosterone

Grant support

This study is supported by grants from the Research Foundation - Flanders (FWO-Vlaanderen grants #G.0332.02 and # G.0404.00) and an unrestricted grant from Roche and GSK Belgium. S.V. is holder of a PhD fellowship and Y.T. is holder of a postdoctoral fellowship from the Research Foundation Flanders (FWO) ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.