Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients: A multicenter study

Laura De Marinis Grasso, Cecilia Martini, M Filopanti, L Olgiati, G Mantovani, Sophie Corbetta, M Arosio, V Gasco, F Bogazzi, S Cannavò, A Colao, D Ferone, G Arnaldi, F Pigliaru, A Peri, G Angeletti, Ml Jaffrain Rea, Ag Lania, A. Spada

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32 Citazioni (Scopus)

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-V and 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. Copyright © 2012 by The Endocrine Society.
Lingua originaleEnglish
pagine (da-a)E165-E165-E172
RivistaTHE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Volume97
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • DNA sequence
  • adult
  • article
  • combination chemotherapy
  • controlled study
  • drug efficacy
  • drug response
  • drug safety
  • drug tolerability
  • drug withdrawal
  • exon
  • female
  • gene deletion
  • gene frequency
  • gene location
  • genetic variability
  • genotype
  • growth hormone receptor
  • human
  • intermethod comparison
  • lipohypertrophy
  • major clinical study
  • male
  • marker gene
  • molecular pathology
  • monotherapy
  • multicenter study
  • multiplex polymerase chain reaction
  • nucleotide sequence
  • outcome assessment
  • patient compliance
  • pegvisomant
  • prediction
  • priority journal
  • side effect
  • single nucleotide polymorphism
  • somatostatin derivative, acromegaly
  • tumor volume

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