Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients : a multicenter study
Articolo
Data di Pubblicazione:
2012
Citazione:
Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients : a multicenter study / M. Filopanti, L. Olgiati, G. Mantovani, S. Corbetta, M. Arosio, V. Gasco, L. De Marinis, C. Martini, F. Bogazzi, S. Cannavò, A. Colao, D. Ferone, G. Arnaldi, F. Pigliaru, A. Peri, G. Angeletti, M.L. Jaffrain Rea, A.G. Lania, A. Spada. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 97:2(2012 Feb), pp. E165-E172.
Abstract:
Context: The influence of full-length GH receptor (GHR) and exon 3-deleted GHR (d3GHR) on responsiveness to pegvisomant (PEG-V) in acromegalic patients is uncertain.
Objective: The aim of the study was to assess the distribution of GHR genotypes in a large series of patients on PEG-V therapy and their influence on treatment efficacy and adverse effects.
Design and Setting: A cross-sectional multicenter pharmacogenetic study was conducted in 16 Italian endocrinology centers of major universities and tertiary care hospitals.
Patients: The study included 127 acromegalic patients enrolled from 2009 to 2010 not cured by previous surgery, radiotherapy, and long-acting somatostatin (SST) analogs, treated with PEG-V.
Intervention and Main Outcome Measure: Sixty-three of 127 patients received combined PEG-V + SST analog therapy. Clinical and hormonal data at diagnosis and before and during PEG-V therapy were inserted in a database. GHR exon 3 deletion and other polymorphisms were genotyped by the coordinator center. Differences in PEG-V dosage required for IGF-I normalization and occurrence of adverse effects between carriers and noncarriers of GHR variants were evaluated.
Results: d3GHR variants were not in Hardy-Weinberg equilibrium (P = 0.008). No association of these variants with PEG-V dose required for IGF-I normalization, adverse effects occurrence, and tumor regrowth was found in patients on PEG-Vand on PEG-V + SST analog treatment. Similar data were obtained considering the GHR variant rs6180.
Conclusions: This study did not confirm a better response of d3GHR to PEG-V treatment in acromegaly. Other studies are needed to determine whether deviation from Hardy-Weinberg equilibrium may indicate an association of d3GHR genotype with poor response to usual treatments.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
gestational-age children; full-lenght isoforms; recombinant human GH ;deficinet adults; final height; polymorphism; exon-3 ; term; D3 ; genotype
Elenco autori:
M. Filopanti, L. Olgiati, G. Mantovani, S. Corbetta, M. Arosio, V. Gasco, L. De Marinis, C. Martini, F. Bogazzi, S. Cannavò, A. Colao, D. Ferone, G. Arnaldi, F. Pigliaru, A. Peri, G. Angeletti, M.L. Jaffrain Rea, A.G. Lania, A. Spada
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