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 van der Klaauw, A. A. Articles by Romijn, J. A. Search for Related Content PubMed PubMed Citation Articles by van der Klaauw, A. A. Articles by Romijn, J. A. Related Collections Neuroendocrinology and Pituitary

Influence of the d3-Growth Hormone (GH) Receptor Isoform on Short-Term and Long-Term Treatment Response to GH Replacement in GH-Deficient Adults

Departments of Endocrinology and Metabolic Diseases (A.A.v.d.K., N.R.B., A.M.P., J.W.A.S., J.A.R.) and Clinical Pharmacy and Toxicology (T.v.d.S., R.B.-P., H.-J.G.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: A. A. van der Klaauw, M.D., Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: a.a.van_der_klaauw{at}lumc.nl.

Objective: Recombinant human GH (rhGH) replacement in adults is aimed at improving signs and symptoms of the adult GH deficiency (GHD) syndrome. In children, a common polymorphism of the GH receptor (exon-3 deletion, d3GHR) increases the response to rhGH replacement. The aim of this study was to assess the effects of this polymorphism on the response to rhGH replacement in adults.

Design: Prospective intervention with rhGH during 1 yr (n = 99) and in a subset during 5 yr (n = 53).

Patients and Methods: The presence of the d3GHR variant was established in GHD patients and linked to short-term and long-term effects of rhGH replacement on IGF-I, lipid metabolism, anthropometric parameters, and bone mineral density.

Results: Fifty-five patients had two wild-type alleles (56%), whereas 38 patients (38%) had one allele and six patients (6%) had two alleles coding the d3GHR isoform. During short-term rhGH replacement, the increase in IGF-I was higher in patients bearing at least one d3GHR allele, compared with those with two wild-type alleles (at an identical mean dose of rhGH). The decrease in total cholesterol and low-density lipoprotein cholesterol was lower in the group bearing at least one d3GHR allele, whereas the increase in high-density lipoprotein cholesterol was higher, compared with patients with the wild-type genotype. In contrast, these differential responses of GHR genotype could not be demonstrated during long-term rhGH replacement.

Conclusion: The d3GHR genotype contributes, at least for some parameters, to the interindividual differences in efficacy of short-term, but not long-term, rhGH replacement in adults with GHD.

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]