Abstract

Objective: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA). Design: The study included short prepubertal SGA children treated with rhGH for 1 or 2 years. Population: Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6·6 ± 2·3 years with a height at –3·0 ± 0·7 SDS at start of rhGH treatment; 193 ethnically matched controls. Methods: The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated. Results: The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0·038 for the first year and P = 0·041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0·034) and in those with the fl/d3 genotype (P = 0·016). Conclusion: Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.