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

Abstract

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. 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. This was cross-sectional and was part of the COPENHAGEN puberty study. The study was conducted at a tertiary center for pediatric endocrinology. Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr. 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. 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. 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 beta-cell compensatory capacity.