Genetic Variations and Drug-Induced Liver Injury in Patients on Simvastatin

Abstract

Drug-induced liver injury, or DILI, is a primary reason for heart failure.  Uridine diphosphate glucuronosyltransferase 1-1 encoded by the UDP glucuronosyltransferase family 1-member A1 gene (UGT1A1) helps prevent DILI by taking part in reactions that conjugate glucuronic acid with bilirubin. UGT1A1 variations are reported to be linked with DILI.  In this study, we investigated the association between genetic variations in UGT1A1 and hepatic adverse effects in patients treated with simvastatin.  Our results show that rs4148325 is not significantly associated with elevated bilirubin levels.  Therefore, our study suggests that genotypic variations in the UGT1A1 gene may be responsible for simvastatin-related increases in bilirubin levels in our patient cohort.  We conclude that genotyping patients on simvastatin for variations in the UGT1A1 gene may not help predict whether these patients are more likely to suffer from liver injury and consequently can change the drug or dose of the drug.