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Submitted on March 29, 2006
Accepted on June 20, 2006
Department of Pediatrics, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain; Medical Unit, Pfizer Spain, Madrid, Spain; WW Medical Endocrine Care, Pfizer GmbH, Germany; WW Endocrine Care Team, Pfizer Health AB, Sweden; Clinical Polyomics, Pfizer Inc, New York, USA
* To whom correspondence should be addressed. E-mail: ancarrascosa{at}vhebron.net.
Context: The d3-growth hormone receptor polymorphism (d3-GHR) has recently been associated with responsiveness to GH therapy.
Objective: To evaluate whether the d3-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in SGA patients.
Design: A two-year 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: 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/day) for 2 yr and 84 were not treated.
Main outcome measures: Previous and two-year follow-up auxologic data were recorded at each hospital, d3-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 (GV) and height-SDS during the first and second years, total two-year height gain (18.5 ± 2.4 cm in d3/d3; 18.4 ± 2.6 in d3/fl; 19.5 ± 2.3 in fl/fl), 
two-year 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-GHR genotypes. In group 1 non-GH-treated patients, neither GV nor height-SDS changed significantly and values were similar in each d3-GHR genotype.
Results in all patients (group 2) were similar to those in group 1.
Conclusion: In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 µg/k/day GH therapy were similar for each d3-GHR genotype carried.
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