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Growth Hormone (GH) Dose, But Not Exon 3-Deleted/Full-Length GH Receptor Polymorphism Genotypes, Influences Growth Response to Two-Year GH Therapy in Short Small-for-Gestational-Age Children

Department of Pediatrics, Institut de Recerca, Hospital Vall d’Hebron, Centre for Biomedical Research on Rare Diseases (Centro de Investigación Biomédica en Red de Enfermedades Raras), Autonomous University, 08035, Barcelona, Spain

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: In short small-for-gestational-age (SGA) patients, the exon 3-deleted(d3)/full-length (fl)-GHR polymorphism was associated with responsiveness to GH therapy (30–48 µg/kg·d); however, these results were not confirmed for higher GH doses (56–66 µg/kg·d). We hypothesized that higher doses would mask the lower dose differences.

Objective: Our objective was to evaluate, in short SGA patients, 2-yr growth response to GH therapy (32.1 ± 3.8 µg/kg·d) according to exon d3/fl-GHR genotypes.

Setting: This was a 2-yr follow-up study.

Patients: There was a total of 60 short SGA children (d3/d3 n = 8, d3/fl n = 23, and fl/fl n = 29). There were 11 children that entered puberty during the second follow-up year. Results were evaluated for all patients (group A1, n = 60, 7.7 ± 2.7 yr) and for patients who remained prepubertal (group A2, n = 49, 6.9 ± 2.2 yr).

Main Outcome Measures: Patients were followed by a single clinical team, and exon d3/fl-GHR genotypes were determined and analyzed in the same hospital.

Results: In groups A1 and A2, growth velocity significantly (P < 0.0001) increased during the first and second years of therapy, as did height SD score (SDS). These increases were similar in each exon d3/fl-GHR genotype. Total 2-yr height gain (cm, SDS) did not differ statistically among genotypes: group A1, 15.0 ± 2.0 cm and 1.15 ± 0.45 SDS in d3/d3, 16.0 ± 2.4 cm and 1.17 ± 0.51 SDS in d3/fl, 16.1 ± 2.4 cm and 1.15 ± 0.53 SDS in fl/fl; and group A2, 15.4 ± 2.0 cm and 1.03 ± 0.42 SDS in d3/d3, 15.6 ± 2.1 cm and 1.22 ± 0.51 in d3/fl, and 16.2 ± 2.6 cm and 1.21 ± 0.56 SDS in fl/fl.

Conclusions: These results did not confirm our hypothesis and show that, in short SGA children, 2-yr growth response to GH therapy 32.1 ± 3.8 µg/kg·d was similar for each exon d3/fl-GHR genotype carried, as occurred in our previous study using 66 µg/kg·d.

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				L. Audi, A. Carrascosa, C. Esteban, M. Fernandez-Cancio, P. Andaluz, D. Yeste, R. Espadero, M. L. Granada, H. Wollmann, L. Fryklund, et al. The exon 3-deleted/full-length Growth Hormone Receptor Polymorphism Does Not Influence the Effect of Puberty or Growth Hormone Therapy on Glucose Homeostasis in Short Non-Growth Hormone-Deficient Small-for-Gestational-Age Children: Results from a Two-Year Controlled Prospective Study J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2709 - 2715. [Abstract] [Full Text] [PDF]