CAG and GGN repeats in AR gene exert combinatorial effects on reproductive parameters in Baltic young male cohort

Abstract

Objectives: The androgen receptor (AR) mediating androgen action is primarily involved in sexual differentiation during embryogenesis, growth of accessory sex organs as well as normal sperm production. Androgen receptor gene (AR) harbours two polymorphic polyglutamine (CAG) and polyglycine (GGN) repeat motifs. We aimed to study individual and combinatorial effect of CAG and GGN repeats on hormonal and testicular parameters in Baltic male cohort. Material and methods: Baltic young male cohort (n=974, 20.1±2.0 yrs, sperm conc. 81.6±73.0 mln/mL); genotyping of CAG and GGN repeats by fluorescently‐labelled PCR; linear regression (CAG and GGN repeat lengths as continuous variables), one‐way analysis of covariance (ANCOVA, CAG and GGN trichotomised as short, medium, and long (i.e., CAG≤21, 22≤CAG≤24, CAG≥25; GGN≤22, GGN=23, GGN≥24), and treated as categorical variables), adjustment for confounders; Mann‐Whitney U‐ (M‐W) and Kruskal‐Wallis (K‐W) tests in the groups of trichotomised CAG and GGN lengths as well as in nine groups of the combinations of short (s), medium (m), and long (l) CAG and GGN repeats (i.e., lCAG–sGGN = long CAG–short GGN, etc.). Results and Conclusion: The median (range) of CAG and GGN repeat lengths were 23 (13‐33) and 23 (9‐28), respectively. Significant positive correlation was identified between CAG and GGN repeats (Pearson's r=0.142, p<0.0001). Men with longer CAG repeat length had significantly lower serum FSH (linear model p=0.002, β=-­‐0.056 IU/L; sCAG vs lCAG, mean(median), 3.24(2.92) vs 2.94(2.53) IU/L, M‐W p=0.014) accompanied with non‐significantly lower sperm concentration (sCAG vs lCAG, 89.0(71.6) vs 80.0 (62.9) mln/mL, M‐W p=0.061). Longer GGN repeats were significantly associated with lower sperm concentration (sGGN vs lGGN, 91.3(68.4) vs 76.2 (60.2) mln/mL, M‐W p=0.027). [...].