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.

dx.doi.org/10.1111/j.1365-2265.2007.02911.x, hdl.handle.net/1765/36035
Clinical Endocrinology
Erasmus MC: University Medical Center Rotterdam

Tauber, M, Ester, W.A, Auriol, F, Molinas, C, Fauvel, J, Caliebe, J, … Hokken-Koelega, A.C.S. (2007). GH responsiveness in a large multinational cohort of SGA children with short stature (NESTEGG) is related to the exon 3 GHR polymorphism. Clinical Endocrinology, 67(3), 457–461. doi:10.1111/j.1365-2265.2007.02911.x