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

A. Carrascosa, C. Esteban, R. Espadero, M. Fernández-Cancio, P. Andaluz, M. Clemente, L. Audí, H. Wollmann, L. Fryklund, L. Parodi

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Abstract

Context: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted full-length GHR) polymorphism (d3-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), Δ 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. Copyright © 2006 by The Endocrine Society.
Original languageEnglish
Pages (from-to)3281-3286
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number9
DOIs
Publication statusPublished - 1 Jan 2006

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