CONTEXT: There is variation in the adrenal androgen levels and clinical findings of children with premature adrenarche (PA). OBJECTIVES: 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. DESIGN AND PATIENTS: 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). MAIN OUTCOME MEASURES: AR gene methylation-weighted CAG(n)(mwCAG(n)) via CAG(n) length and X-chromosome inactivation analysis and clinical phenotype were determined. SETTING: The study took place at a university hospital. RESULTS: 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). CONCLUSIONS: The AR gene CAG(n) polymorphism may have a significant role in the pathogenesis of PA, especially in lean children.
CONTEXT: There is variation in the adrenal androgen levels and clinical findings of children with premature adrenarche (PA). OBJECTIVES: 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. DESIGN AND PATIENTS: 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). MAIN OUTCOME MEASURES: AR gene methylation-weighted CAG(n)(mwCAG(n)) via CAG(n) length and X-chromosome inactivation analysis and clinical phenotype were determined. SETTING: The study took place at a university hospital. RESULTS: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 PAchildren with lower BMI compared with PAchildren 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 PAchildren with lower BMI compared with healthy children with same BMI (P = 0.004). CONCLUSIONS: The AR gene CAG(n) polymorphism may have a significant role in the pathogenesis of PA, especially in lean children.
Authors: Claire E Campbell; Adam F Mezher; J Michael Tyszka; Bonnie J Nagel; Sandrah P Eckel; Megan M Herting Journal: Psychoneuroendocrinology Date: 2021-11-24 Impact factor: 4.905
Authors: Judith S Brand; Maroeska M Rovers; Bu B Yeap; Harald J Schneider; Tomi-Pekka Tuomainen; Robin Haring; Giovanni Corona; Altan Onat; Marcello Maggio; Claude Bouchard; Peter C Y Tong; Richard Y T Chen; Masahiro Akishita; Jourik A Gietema; Marie-Hélène Gannagé-Yared; Anna-Lena Undén; Aarno Hautanen; Nicolai P Goncharov; Philip Kumanov; S A Paul Chubb; Osvaldo P Almeida; Hans-Ulrich Wittchen; Jens Klotsche; Henri Wallaschofski; Henry Völzke; Jussi Kauhanen; Jukka T Salonen; Luigi Ferrucci; Yvonne T van der Schouw Journal: PLoS One Date: 2014-07-14 Impact factor: 3.240