Androgen receptor gene CAG repeat polymorphism and X-chromosome inactivation in children with premature adrenarche

There is variation in the adrenal androgen levels and clinical findings of children with premature adrenarche (PA).

We hypothesized that androgen sensitivity, indicated by the length of CAG repeat in the X-chromosomal androgen receptor (AR) gene has a role in the polygenic pathogenesis of PA.

We performed a cross-sectional association study among 73 Finnish Caucasian children with PA (10 boys and 63 girls) and 97 age- and gender-matched healthy controls (18 boys and 79 girls).

AR gene methylation-weighted CAG(n)(mwCAG(n)) via CAG(n) length and X-chromosome inactivation analysis and clinical phenotype were determined.

The study took place at a university hospital.

PA subjects had significantly shorter mwCAG(n) than controls [mean difference (95% confidence interval); 0.76 (0.14-1.38); P = 0.017]. AR gene mwCAG(n) did not correlate with androgen or SHBG levels in either group. In children with PA, mwCAG(n) correlated positively with body mass index (BMI) (tau = 0.19; P = 0.02). The mean of mwCAG(n) was significantly shorter in PA children with lower BMI compared with PA children with higher BMI [BMI sd score < 0.79, n = 35, vs. BMI sd score > 0.79, n = 36; 1.13 (0.38-1.87), P = 0.004] and in PA children with lower BMI compared with healthy children with same BMI (P = 0.004).

The AR gene CAG(n) polymorphism may have a significant role in the pathogenesis of PA, especially in lean children.