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Androgen Receptor CAG Repeat Length Is Associated With Body Fat and Serum SHBG in Boys: A Prospective Cohort Study

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Background: Longer androgen receptor gene CAG trinucleotide repeats, AR (CAG)n, have been associated with reduced sensitivity of the androgen receptor (AR) in vitro as well as in humans. Furthermore, short AR (CAG)n have been associated with premature adrenarche. Objective: The aim of the study was to evaluate associations between the AR (CAG)n polymorphism and development of pubic hair, levels of androgens, and body fat content in healthy boys. Methods: A longitudinal study of 78 healthy boys (age 6.2-12.4 years at inclusion) from the COPENHAGEN Puberty Study was conducted with clinical examinations and blood samples drawn every 6 months. The AR (CAG)n length was established by direct DNA sequencing and reproductive hormones were measured in serum by standardized analyses. Results: Median AR (CAG)n length was 22 (range, 17-30). Before puberty (at 10 years of age), boys with long CAG repeats (CAG ≥24) had lower levels of SHBG (88 vs 125 nmol/L) (P <.05) and a nonsignificant trend toward higher median skinfold thickness (41 vs 31 mm) (P = .06) compared with boys with an average number of CAG repeats (CAG 21-23). In contrast, the inverse association was observed at puberty (at 12 years of age) in boys with short CAG repeats (CAG 17-20) (P <.05). Serum levels of LH and testosterone (at 12 years) were significantly higher in boys with long CAG repeats compared with boys with an average number of CAG repeats (P = .05). Conclusion: The observed associations between AR (CAG)n and peripubertal fat accumulation and serum SHBG concentrations indicate that this genetic polymorphism may influence the androgen-dependent fine-tuning of metabolic and reproductive factors at a young age.
Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number3
Pages (from-to)E605-9
ISSN0021-972X
DOIs
Publication statusPublished - 2013

ID: 38278555