This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pilotta, A. Articles by Buzi, F. Search for Related Content PubMed PubMed Citation Articles by Pilotta, A. Articles by Buzi, F. Related Collections Neuroendocrinology and Pituitary Pediatric Endocrinology

Common Polymorphisms of the Growth Hormone (GH) Receptor Do Not Correlate with the Growth Response to Exogenous Recombinant Human GH in GH-Deficient Children

Department of Pediatrics (A.P., M.F., B.F., E.P., L.D.N., F.B.), Institute of Molecular Medicine A. Nocivelli (P.M.), and Section of Medical Statistics (G.P.), University of Brescia, 25123 Brescia, Italy

Address all correspondence and requests for reprints to: Dr. F. Buzi, Clinica Pediatrica dell’Università di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy. E-mail: fbuzi{at}med.unibs.it.

Context: GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH).

Objective: The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children.

Design: This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment).

Setting: This study was performed at a referral center.

Patients: Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; SD, 3.96) were studied.

Intervention: Patients were treated with rhGH (0.2 mg/kg·wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer.

Main Outcome Measures: Before the start of treatment, the mean height (Ht) SD score was –1.93 (SD, 0.70), and the mean GV SD score was –1.49 (SD, 1.26).

Results: The posttreatment (first 12 months) mean GV SD score was 3.55 (SD, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes.

Conclusion: The most common GHR polymorphisms, alone or in association, do not appear to affect the growth response to rhGH in GHD children.

This article has been cited by other articles:

				O R Adetunji, I A MacFarlane, M Javadpour, A Alfirevic, M Pirmohamed, and J C Blair The d3/fl-GH receptor gene polymorphism does not influence quality of life and body composition in GH-deficient adults receiving GH replacement therapy Eur. J. Endocrinol., October 1, 2009; 161(4): 541 - 546. [Abstract] [Full Text] [PDF]

				M. J. E. Wassenaar, O. M. Dekkers, A. M. Pereira, J. M. Wit, J. W. Smit, N. R. Biermasz, and J. A. Romijn Impact of the Exon 3-Deleted Growth Hormone (GH) Receptor Polymorphism on Baseline Height and the Growth Response to Recombinant Human GH Therapy in GH-Deficient (GHD) and Non-GHD Children with Short Stature: A Systematic Review and Meta-Analysis J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3721 - 3730. [Abstract] [Full Text] [PDF]

				P. Kamenicky, C. Dos Santos, C. Espinosa, S. Salenave, F. Galland, Y. Le Bouc, P. Maison, P. Bougneres, and P. Chanson D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly Eur. J. Endocrinol., August 1, 2009; 161(2): 231 - 235. [Abstract] [Full Text] [PDF]

				E. J. L. Barbosa, J. Palming, C. A. M. Glad, H. Filipsson, J. Koranyi, B.-A. Bengtsson, L. M. S. Carlsson, C. L. Boguszewski, and G. Johannsson Influence of the Exon 3-Deleted/Full-Length Growth Hormone (GH) Receptor Polymorphism on the Response to GH Replacement Therapy in Adults with Severe GH Deficiency J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 639 - 644. [Abstract] [Full Text] [PDF]

				G. Kenth, J. A M. Mergelas, and C. G. Goodyer Developmental changes in the human GH receptor and its signal transduction pathways J. Endocrinol., July 1, 2008; 198(1): 71 - 82. [Abstract] [Full Text] [PDF]

				A. A. van der Klaauw, T. van der Straaten, R. Baak-Pablo, N. R. Biermasz, H.-J. Guchelaar, A. M. Pereira, J. W. A. Smit, and J. A. Romijn Influence of the d3-Growth Hormone (GH) Receptor Isoform on Short-Term and Long-Term Treatment Response to GH Replacement in GH-Deficient Adults J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2828 - 2834. [Abstract] [Full Text] [PDF]

				B. Raz, M. Janner, V. Petkovic, D. Lochmatter, A. Eble, M. T. Dattani, P. C. Hindmarsh, C. E. Fluck, and P. E. Mullis Influence of Growth Hormone (GH) Receptor Deletion of Exon 3 and Full-Length Isoforms on GH Response and Final Height in Patients with Severe GH Deficiency J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 974 - 980. [Abstract] [Full Text] [PDF]

				A. Carrascosa, L. Audi, M. Fernandez-Cancio, C. Esteban, P. Andaluz, E. Vilaro, M. Clemente, D. Yeste, M. A. Albisu, and M. Gussinye The Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism Did Not Influence Growth Response to Growth Hormone Therapy over Two Years in Prepubertal Short Children Born at Term with Adequate Weight and Length for Gestational Age J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 764 - 770. [Abstract] [Full Text] [PDF]

				A. Carrascosa, L. Audi, C. Esteban, M. Fernandez-Cancio, P. Andaluz, M. Gussinye, M. Clemente, D. Yeste, and M. A. Albisu 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 J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 147 - 153. [Abstract] [Full Text] [PDF]

				F. Schreiner, S. Stutte, P. Bartmann, B. Gohlke, and J. Woelfle Association of the Growth Hormone Receptor d3-Variant and Catch-up Growth of Preterm Infants with Birth Weight of Less Than 1500 Grams J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4489 - 4493. [Abstract] [Full Text] [PDF]

				R. G Rosenfeld Pharmacogenomics and pharmacoproteomics in the evaluation and management of short stature Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S27 - S31. [Abstract] [Full Text] [PDF]

				R. B. Jensen, S. Vielwerth, T. Larsen, G. Greisen, H. Leffers, and A. Juul The Presence of the d3-Growth Hormone Receptor Polymorphism Is Negatively Associated with Fetal Growth but Positively Associated with Postnatal Growth in Healthy Subjects J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2758 - 2763. [Abstract] [Full Text] [PDF]

				G. Kenth, Z. Shao, D. E. C. Cole, and C. G. Goodyer Relationship of the Human Growth Hormone Receptor Exon 3 Genotype with Final Adult Height and Bone Mineral Density J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 725 - 728. [Abstract] [Full Text] [PDF]

				L. Audi, C. Esteban, A. Carrascosa, R. Espadero, A. Perez-Arroyo, R. Arjona, M. Clemente, H. Wollmann, L. Fryklund, L. A. Parodi, et al. Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism Genotype Frequencies in Spanish Short Small-for-Gestational-Age (SGA) Children and Adolescents (n = 247) and in an Adult Control Population (n = 289) Show Increased fl/fl in Short SGA J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5038 - 5043. [Abstract] [Full Text] [PDF]

				W. F. Blum, K. Machinis, E. P. Shavrikova, A. Keller, H. Stobbe, R. W. Pfaeffle, and S. Amselem The Growth Response to Growth Hormone (GH) Treatment in Children with Isolated GH Deficiency Is Independent of the Presence of the Exon 3-Minus Isoform of the GH Receptor J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4171 - 4174. [Abstract] [Full Text] [PDF]

				A. Carrascosa, C. Esteban, R. Espadero, M. Fernandez-Cancio, P. Andaluz, M. Clemente, L. Audi, H. Wollmann, L. Fryklund, L. Parodi, et al. The d3/fl-Growth Hormone (GH) Receptor Polymorphism Does Not Influence the Effect of GH Treatment (66 {micro}g/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 J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3281 - 3286. [Abstract] [Full Text] [PDF]