A Gilbert's syndrome UGT1A1 variant confers susceptibility to tranilast-induced hyperbilirubinemia.
Pharmacogenomics J
; 4(1): 49-53, 2004.
Article
em En
| MEDLINE
| ID: mdl-14647407
ABSTRACT
Tranilast (N-(3'4'-demethoxycinnamoyl)-anthranilic acid (N-5)) is an investigational drug for the prevention of restenosis following percutaneous transluminal coronary revascularization. An increase in bilirubin levels was observed in 12% of patients upon administration of tranilast in a phase III clinical trial. To identify the potential genetic factors that may account for the drug-induced hyperbilirubinemia, we examined polymorphisms in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene in over a thousand patients. Our results suggested that the TA repeat polymorphism in UGT1A1, which predisposes some individuals to Gilbert's syndrome, predicted the susceptibility to tranilast-induced hyperbilirubinemia. The (TA)(7)/(TA)(7) genotype was present in 39% of the 127 hyperbilirubinemic patients vs 7% of the 909 controls (P=2 x 10(-22)). Rapid identification of genetic factors accounting for the observed adverse effect during the course of a double-blind clinical trial demonstrated the potential application of pharmacogenetics in the clinical development of safe and effective medicines.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glucuronosiltransferase
/
Predisposição Genética para Doença
/
Ortoaminobenzoatos
/
Doença de Gilbert
/
Hiperbilirrubinemia
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos