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

Research output: Contribution to journalArticle

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 (67 μg/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)) (4.4 mmol/L (0.6) vs. 4.2 mmol/L (0.7)) (p = 0.03), C-peptide (232.1 pmol/L (168.8–304.1) vs. 185.1 pmol/L (137.7–253.9)) (p = 0.04) and insulin (19.2 pmol/L (11.8–32.2)) vs. (13.7 pmol/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.

Details

Authors
  • Mathilde Gersel Wegmann
  • Ajay Thankamony
  • Edna Roche
  • Hilary Hoey
  • Jeremy Kirk
  • Guftar Shaikh
  • Sten A. Ivarsson
  • Olle Söder
  • David B. Dunger
  • Anders Juul
  • Rikke Beck Jensen
Organisations
External organisations
  • University of Copenhagen
  • University of Cambridge
  • Trinity College Dublin
  • Birmingham Children's Hospital
  • Royal Hospital for Sick Children, Glasgow
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • Body composition, Exon3-deleted growth hormone receptor gene polymorphism, Growth, Growth hormone treatment, Insulin metabolism - insulin sensitivity, Small for gestational age
Original languageEnglish
Pages (from-to)45-51
Number of pages7
JournalGrowth Hormone and IGF Research
Volume35
Publication statusPublished - 2017 Aug 1
Publication categoryResearch
Peer-reviewedYes