The exon3-deleted growth hormone receptor gene polymorphism (d3-GHR) is associated with insulin and spontaneous growth in short SGA children (NESGAS)

Abstract

Objective: The effect of a common polymorphism in the Growth Hormone (GH) receptor (d3-GHR) gene on growth, metabolism and body composition was examined in short children born small for gestational age (SGA) on GH treatment.

Design: In 96 prepubertal, short SGA children treated with high-dose GH (67μg/kg/day) in the NESGAS study, insulin sensitivity (IS), insulin secretion and disposition index (DI) were determined during the first year of treatment. Body composition was analysed by DXA. The d3-GHR locus was determined by simple multiplex PCR.

Results: At baseline, children in the d3-GHR group (d3/fl (n=37), d3/d3 (n=7)) had significantly lower IS (median (25-75 percentile)) (223.3% (154.4-304.8)) vs. (269.7% (185.1-356.7)) (p=0.03) and higher concentrations of glucose (mean (SD)) (4.4mmol/L (0.6) vs. 4.2mmol/L (0.7)) (p=0.03), C-peptide (232.1pmol/L (168.8-304.1) vs. 185.1pmol/L (137.7-253.9)) (p=0.04) and insulin (19.2pmol/L (11.8-32.2)) vs. (13.7pmol/L (9.3-20.8)) (p=0.04) compared to children homozygous for the full length allele (fl/fl-GHR (n=52)). There were no differences in DI or insulin secretion. Postnatal, spontaneous growth was significantly greater in the d3-GHR group compared to the fl/fl-GHR group (p=0.02). There were no significant differences in growth response, body composition or metabolism after one year of GH therapy.

Conclusion: Short SGA children carrying the d3-GHR polymorphism had increased spontaneous growth, lower IS and a compensatory increase in glucose, C-peptide and insulin before GH therapy compared to children homozygous for the full-length allele.

Keywords: Body composition; Exon3-deleted growth hormone receptor gene polymorphism; Growth; Growth hormone treatment; Insulin metabolism - insulin sensitivity; Small for gestational age.