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

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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.

Original languageEnglish
JournalGrowth Hormone & I G F Research
Volume35
Pages (from-to)45-51
Number of pages7
ISSN1096-6374
DOIs
Publication statusPublished - Aug 2017

    Research areas

  • Body Height/drug effects, Child, Child Development/drug effects, Child, Preschool, Exons, Female, Genetic Association Studies, Growth Disorders/drug therapy, Human Growth Hormone/therapeutic use, Humans, Infant, Newborn, Infant, Small for Gestational Age/growth & development, Insulin/blood, Male, Polymorphism, Genetic, Protein Isoforms/genetics, Receptors, Somatotropin/genetics, Remission, Spontaneous, Sequence Deletion

ID: 58111065