title: Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients: a multicenter study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  A cross-sectional multicenter pharmacogenetic study was conducted in 16 Italian endocrinology centers of major universities and tertiary care hospitals.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: University of Milan, Department of Medical Sciences, Via F. Sforza, 35, Milan 20122, Italy. anna.spada@unimi.it.
authors.forename: M
authors.initials: M
authors.lastname: Filopanti
authors.forename: L
authors.initials: L
authors.lastname: Olgiati
authors.forename: G
authors.initials: G
authors.lastname: Mantovani
authors.forename: S
authors.initials: S
authors.lastname: Corbetta
authors.forename: M
authors.initials: M
authors.lastname: Arosio
authors.forename: V
authors.initials: V
authors.lastname: Gasco
authors.forename: L
authors.initials: L
authors.lastname: De Marinis
authors.forename: C
authors.initials: C
authors.lastname: Martini
authors.forename: F
authors.initials: F
authors.lastname: Bogazzi
authors.forename: S
authors.initials: S
authors.lastname: Cannavò
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: D
authors.initials: D
authors.lastname: Ferone
authors.forename: G
authors.initials: G
authors.lastname: Arnaldi
authors.forename: F
authors.initials: F
authors.lastname: Pigliaru
authors.forename: A
authors.initials: A
authors.lastname: Peri
authors.forename: G
authors.initials: G
authors.lastname: Angeletti
authors.forename: M L
authors.initials: ML
authors.lastname: Jaffrain-Rea
authors.forename: A G
authors.initials: AG
authors.lastname: Lania
authors.forename: A
authors.initials: A
authors.lastname: Spada
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D000236:Adenoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; C406545:pegvisomant