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Impact of the Growth Hormone Receptor Exon 3 Deletion Gene Polymorphism on Glucose Metabolism, Lipids, and Insulin-Like Growth Factor-I Levels during Puberty

Departments of Growth and Reproduction (K.S., L.A., H.L., A.J.) and Biochemistry (L.H.) and Muscle Research Centre (T.M.-A., N.J.A.-A.), Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; and Department of Biomedical Sciences (J.W.H.), Centre of Healthy Ageing, University of Copenhagen, DK-2200 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Kaspar Sorensen, M.D., Department of Growth and Reproduction, GR-5064, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: kaspar.soerensen{at}rh.regionh.dk.

Context: The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH.

Objective: The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents.

Design: This was cross-sectional and was part of the COPENHAGEN puberty study.

Setting: The study was conducted at a tertiary center for pediatric endocrinology.

Participants: Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5–16.1 yr.

Interventions: Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels.

Results: Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels.

Conclusion: The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic β-cell compensatory capacity.