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The d3/fl-Growth Hormone (GH) Receptor Polymorphism Does Not Influence the Effect of GH Treatment (66 µg/kg per Day) or the Spontaneous Growth in Short Non-GH-Deficient Small-for-Gestational-Age Children: Results from a Two-Year Controlled Prospective Study in 170 Spanish Patients

Department of Pediatrics (A.C., C.E., M.F.-C., P.A., M.C., L.A.), Hospital Vall d’Hebron, Autonomous University, 08035 Barcelona, Spain; Medical Unit (R.E.), Pfizer Spain, 28108 Madrid, Spain; WW Medical Endocrine Care (H.W.), Pfizer GmbH, 76139 Karlsruhe, Germany; WW Endocrine Care Team (L.F.), Pfizer Health AB, 191 90 Sollentuna, Sweden; and Clinical Polyomics (L.P.), Pfizer Inc., New York, New York 10017

Address all correspondence and requests for reprints to: Antonio Carrascosa, Servicio de Pediatría, Unidad de Endocrinología, Hospital Maternoinfantil Vall d’Hebron, Paseo Vall d’Hebron 119, 08035 Barcelona, Spain. E-mail: ancarrascosa{at}vhebron.net.

Context: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy.

Objective: The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients.

Design: This was a 2-yr prospective, controlled, randomized trial.

Setting: Thirty Spanish hospitals participated. Auxologic and GH secretion evaluation was hospital based, whereas molecular analyses and auxologic data computation were centralized.

Patients: Patients included 170 short SGA children: 140 remained prepubertal and 30 entered puberty during the second follow-up year.

Intervention: Eighty-six were treated with GH (66 µg/kg·d) for 2 yr and 84 were not treated.

Main Outcome Measures: Previous and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR genotypes determined, and data analyzed for patients who remained prepubertal (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group 2).

Results: In group 1 GH-treated patients, growth velocity, and height-SD score during the first and second years, total 2-yr height gain (18.5 ± 2.4 cm in d3/d3; 18.4 ± 2.6 in d3/fl; 19.5 ± 2.3 in fl/fl), 2-yr height increase (9.1 ± 2.4 cm in d3/d3; 9.4 ± 3.0 in d3/fl; 10.4 ± 2.1 in fl/fl), first-year growth prediction and studentized residual values (0.08 ± 1.26 in d3/d3; 0.28 ± 1.21 in d3/fl; 0.67 ± 0.95 in fl/fl) did not differ among the d3/fl-GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor height-SD score changed significantly, and values were similar in each d3/fl-GHR genotype. Results in all patients (group 2) were similar to those in group 1.

Conclusions: In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 µg/k·d GH therapy were similar for each d3/fl-GHR genotype carried.

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