The Journal of clinical endocrinology and metabolism · 2010
Pegvisomant-induced liver injury is related to the UGT1A1*28 polymorphism of Gilbert's syndrome.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bernabeu Ignacio, Marazuela Mónica, Lucas Tomás, Loidi Lourdes, Alvarez-Escolá Cristina, Luque-Ramírez Manuel, Fernandez-Rodriguez Eva, Paniagua Amalia-Elisa, Quinteiro Celsa, Casanueva Felipe F
Аннотация
CONTEXT: 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.
DESIGN AND SETTING: A cross-sectional study was conducted in four Spanish university hospitals.
PATIENTS: 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.
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.
DESIGN AND SETTING: A cross-sectional study was conducted in four Spanish university hospitals.
PATIENTS: 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.
Предметные рубрики MeSH
AcromegalyAdultAgedAlcohol DrinkingDNA PrimersFemaleGenetic Carrier ScreeningGenotypeGilbert DiseaseGlucuronosyltransferaseHomozygoteHuman Growth HormoneHumansLiver DiseasesMaleMiddle AgedPolymerase Chain ReactionPolymorphism, GeneticReceptors, SomatotropinRegression AnalysisSex CharacteristicsTATA BoxUGT1A1 Enzyme