The exon 3 deleted growth hormone receptor gene is associated with small birth size and early pubertal onset in healthy boys

TY - JOUR

T1 - The exon 3 deleted growth hormone receptor gene is associated with small birth size and early pubertal onset in healthy boys

AU - Sørensen, Kaspar

AU - Aksglæde, Lise

AU - Petersen, JH

AU - Leffers, H

AU - Juul, A

PY - 2010/6

Y1 - 2010/6

N2 - Context: The GH/IGF-I axis influences gonadal development and function. Recently, a deletion of exon 3 in the GH receptor gene (GHRd3) has been linked to increased responsiveness to GH. Objective: Our objective was to evaluate the influence of the GHRd3 gene on birth size and pubertal onset. Design and Setting: We conducted a cross-sectional study, part of The COPENHAGEN Puberty Study, at a tertiary center for pediatric endocrinology. Participants: Participants included 618 healthy boys aged 6.1-19.8 yr. Main Outcome Measures: We assessed pubertal onset by genital staging and testicular palpation andparental reported birth weight and length.GHR genotypes were determined by multiplex PCR. Results: Age at onset of genital development (G2+) was significantly earlier in the GHRd3 homozygotes (GHRd3/d3) [10.86 (10.35-11.37) yr, mean (95% confidence interval)] compared with the full-length homozygotes (GHRfl/fl) [11.76 (11.35-12.00) yr, P=0.002]. The odds ratio of having detectable testosterone levels for a given age was significantly higher in GHRd3/d3 compared with GHRfl/fl group (odds ratio = 3.1; 95% confidence interval = 1.2- 8.9; P = 0.036). The GHRd3/d3 group the higher prepubertal IGF-I levels compared with the GHRfl/fl group (9.2% (0.1-18.1%), P = 0.048) after adjustment for IGF-binding protein-3 levels. Lower gestational-age-adjusted birth weight and length were found in the GHRd3/d3 group compared with the GHRfl/fl group and the GHRfl/d3 group, respectively (all P ≤ 0.018). Conclusion: TheGHRd3/d3 genotype was associated with smaller birth size and earlier age at pubertal onset compared with the GHRfl/fl genotype. Thus, this common polymorphism could play a role for prenatal growth and gonadal development in boys.

AB - Context: The GH/IGF-I axis influences gonadal development and function. Recently, a deletion of exon 3 in the GH receptor gene (GHRd3) has been linked to increased responsiveness to GH. Objective: Our objective was to evaluate the influence of the GHRd3 gene on birth size and pubertal onset. Design and Setting: We conducted a cross-sectional study, part of The COPENHAGEN Puberty Study, at a tertiary center for pediatric endocrinology. Participants: Participants included 618 healthy boys aged 6.1-19.8 yr. Main Outcome Measures: We assessed pubertal onset by genital staging and testicular palpation andparental reported birth weight and length.GHR genotypes were determined by multiplex PCR. Results: Age at onset of genital development (G2+) was significantly earlier in the GHRd3 homozygotes (GHRd3/d3) [10.86 (10.35-11.37) yr, mean (95% confidence interval)] compared with the full-length homozygotes (GHRfl/fl) [11.76 (11.35-12.00) yr, P=0.002]. The odds ratio of having detectable testosterone levels for a given age was significantly higher in GHRd3/d3 compared with GHRfl/fl group (odds ratio = 3.1; 95% confidence interval = 1.2- 8.9; P = 0.036). The GHRd3/d3 group the higher prepubertal IGF-I levels compared with the GHRfl/fl group (9.2% (0.1-18.1%), P = 0.048) after adjustment for IGF-binding protein-3 levels. Lower gestational-age-adjusted birth weight and length were found in the GHRd3/d3 group compared with the GHRfl/fl group and the GHRfl/d3 group, respectively (all P ≤ 0.018). Conclusion: TheGHRd3/d3 genotype was associated with smaller birth size and earlier age at pubertal onset compared with the GHRfl/fl genotype. Thus, this common polymorphism could play a role for prenatal growth and gonadal development in boys.

U2 - 10.1210/jc.2009-2484

DO - 10.1210/jc.2009-2484

M3 - Journal article

C2 - 20382688

SN - 0021-972X

VL - 95

SP - 2819

EP - 2826

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 6

ER -