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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Audí, L. Search for Related Content PubMed PubMed Citation Articles by Audí, L. Related Collections Neuroendocrinology and Pituitary Pediatric Endocrinology Metabolism

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

Department of Pediatrics (L.A., C.E., A.C., A.P.-A., R.A., M.C.), 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, 76032 Karlsruhe, Germany; WW Endocrine Care Team (L.F.), Pfizer Health AB, 191–90 Sollentuna, Sweden; and Clinical Polyomics (L.A.P.), Pfizer Inc, New York, New York 10017

Address all correspondence and requests for reprints to: Laura Audí, Unidad Investigación Endocrinología Pediátrica, Hospital Vall d’Hebron, Paseo Vall d’Hebron 119, 08035 Barcelona, Spain. E-mail: laudi{at}ir.vhebron.net.

Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy.

Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations.

Design: An adult control population with heights normally distributed (ACPNH) between –2 and +2 SD score (SDS) and a short non-GH-deficient SGA child population were selected.

Setting: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH.

Controls and Patients: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients.

Main Outcome Measures: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital.

Results: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height –1 SDS and –2 SDS, n = 60).

Conclusions: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.

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]

				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]

				M. Mercado, B. Gonzalez, C. Sandoval, Y. Esquenazi, F. Mier, G. Vargas, A. L. E. de los Monteros, and E. Sosa Clinical and Biochemical Impact of the d3 Growth Hormone Receptor Genotype in Acromegaly J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3411 - 3415. [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]

				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]

				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. 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]