The androgen receptor (AR) harbors a variable repeat number of glutamine residues codified by (CAG)n, which seems to inversely affect AR transcriptional activity. We assessed whether (CAG)n affects the sequence of the androgen-sensitive pubertal events and body composition in prepubertal girls.
Design, Setting, Participants, and Interventions
Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (approximately 50% girls) from a university clinic in Santiago, Chile. Cases were girls with high dehydroepiandrosterone sulfate (DHEAS; >42 μg/dL; HD) at age 7.0 (±0.4) years (n = 58). On follow-up, 32 of them had thelarche (TB2) before the age of pubarche (PH2) and 26 had PH2 before the age of TB2. As controls, 107 age-matched girls with normal DHEAS (≤42 μg/dL; ND) were selected.
Main Outcome Measures
Methylation-weighted mean (CAG)n (mw[CAG]n) was calculated through X-chromosome methylation-sensitive enzyme restriction and polymerase chain reaction followed by automated capillary electrophoresis in peripheral blood DNA.
Girls with HD and PH2 before the age of TB2 showed a trend to higher frequency (7/26, 26.9%) of mw(CAG)n <20 compared with ND girls (12/107; 11.2%; P = .087). Accordingly, a direct correlation between age of PH2 and mw(CAG)n was observed in HD (r = 0.352; P = .007) and in ND girls (r = 0.207; P = .033). Moreover, HD girls with mw(CAG)n less than 20 had lower waist circumference and waist/height ratio than HD girls with mw(CAG)n from 20 to less than 25 (P = .027 and P = .012, respectively) at age of DHEAS determination.
Our results suggest that a greater transcriptional activity of the AR, given by short number of CAG repeats, might favor the onset of pubarche and reduce central adiposity in prepubertal girls with HD.
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Published online: December 11, 2018
The authors indicate no conflicts of interest.
© 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.