Genetic Variation of Follicle-Stimulating Hormone Action Is Associated With Age at Testicular Growth in Boys
Author
dc.contributor.author
Busch, Alexander S.
Author
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Hagen, Casper P.
Author
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Main, Katharina M.
Author
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Pereira Scalabrino, Ana
Author
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Corvalán Aguilar, Camila
Author
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Almstrup, Kristian
Author
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Mericq, Verónica
Author
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Juul, Anders
Admission date
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2017-09-26T14:32:26Z
Available date
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2017-09-26T14:32:26Z
Publication date
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2017
Cita de ítem
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J Clin Endocrinol Metab, May 2017, 102(5):1740–1749
es_ES
Identifier
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10.1210/jc.2016-4013
Identifier
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https://repositorio.uchile.cl/handle/2250/145076
Abstract
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Context: Although genetic factors play a pivotal role in male pubertal timing, genome-wide association
studies have identified only a few loci. Genetic variation of follicle-stimulating hormone (FSH) action
affects adult reproductive parameters and female pubertal timing.
Objective: To investigate whether genetic variation affecting FSH action is associated with onset of
puberty in boys.
Design: Cross-sectional and longitudinal study of two cohorts of healthy boys.
Setting: This was a population-based study.
Patients or Other Participants: Danish (n = 1130) and Chilean (n = 424) boys were followed through
puberty and genotyped for FSHB c.-211G.T, FSHR c.-29A.G, and FSHR c.2039G.A.
Main Outcome Measures: Clinical pubertal staging including orchidometry, anthropometry, and
serum gonadotropin levels.
Results: Although the cohorts differed markedly (e.g., body composition and genotype frequencies),
genetic variation affecting FSH production (FSHB c.-211G.T) was associated with age at pubertal onset,
as assessed by testicular enlargement, in both cohorts. The effect appeared further modified by coexistence
of genetic variation affecting FSH sensitivity (FSHR c.-29G.A): After correcting for body mass
index (BMI), boys with a ligand-receptor variant combination resulting in weak FSH action (i.e., FSHB
c.-211GT/TT and FSHR c.-29AA) entered puberty 0.64 years [95% confidence interval (CI), 0.12 to 1.17 years;
Denmark] and 0.94 years (95% CI, 0.00 to 1.88 years; Chile) later than boys with the most effective
FSH action. Effects explained 1.7% (Denmark) and 1.5% (Chile) of the variance. In addition, BMI
z score was negatively associated with pubertal timing (b = 20.35 years in both cohorts), explaining
17.2% (Denmark) and 7.2% (Chile) of the variance.
Conclusion: In two ethnically distinct populations, we independently identified an association of
two genetic loci with male pubertal timing.