title: Pegvisomant-induced liver injury is related to the UGT1A1*28 polymorphism of Gilbert's syndrome.
abstract: BACKGROUND
  Pegvisomant (PEG) therapy has been associated with drug-induced liver dysfunction in acromegalic patients. The mechanism of its toxicity remains unknown.
  
  
  OBJECTIVE
  The primary objective was to determine whether or not the UGT1A1*28 polymorphism associated with Gilbert's syndrome influences the development of liver dysfunction during PEG treatment.
  
  
  METHODS
  A cross-sectional study was conducted in four Spanish university hospitals.
  
  
  METHODS
  Thirty-six acromegalic patients with active disease, resistant to somatostatin analogs, participated.
  
  
  RESULTS
  The prevalence of the UGT1A1*28 homozygous and heterozygous genotypes in acromegalic patients was 14 and 44%, respectively. Ten patients (28%) developed liver function test (LFT) abnormalities. There was a tendency for more frequent liver function abnormalities in males (70% males vs. 30% females, P = 0.058). Carriers of the UGT1A1*28 polymorphism had a higher incidence of LFT abnormalities than the UGT1A1 wild type (43% carriers vs. 7% wild type, P = 0.024). This difference persisted when adjusted in an all-factors multiple regression analysis [coefficient of determination (R(2)) = 0.463; P = 0.008] for age, gender, alcohol consumption, and UGT1A1*28 polymorphism. A stepwise multivariate likelihood binary logistic regression analysis (R(2) = 0.40; P = 0.003) identified male gender (beta = 7.21; P = 0.033) and UGT1A1*28 polymorphism (beta = 14.1; P = 0.028) as the only significant predictors for the development of LFT abnormalities.
  
  
  CONCLUSIONS
  The UGT1A1*28 genotype and male gender predict an increased incidence of LFT abnormalities during PEG therapy in acromegaly.
authors.affiliation: Endocrinology Division, Complejo Hospitalario Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
authors.forename: Tomás
authors.initials: T
authors.lastname: Lucas
authors.forename: Lourdes
authors.initials: L
authors.lastname: Loidi
authors.forename: Cristina
authors.initials: C
authors.lastname: Alvarez-Escolá
authors.forename: Manuel
authors.initials: M
authors.lastname: Luque-Ramírez
authors.forename: Eva
authors.initials: E
authors.lastname: Fernandez-Rodriguez
authors.forename: Amalia-Elisa
authors.initials: AE
authors.lastname: Paniagua
authors.forename: Celsa
authors.initials: C
authors.lastname: Quinteiro
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics; D017931:DNA Primers; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D005878:Gilbert Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors; D012044:Regression Analysis; D012727:Sex Characteristics; D016385:TATA Box / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D017931:DNA Primers; D014453:Glucuronosyltransferase; D019382:Human Growth Hormone; D011986:Receptors, Somatotropin; D000099148:UGT1A1 Enzyme; C406545:pegvisomant