Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in glucuronidation and risk for acetaminophen-induced liver injury. Human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen UGT enzymes. Only three linked single nucleotide polymorphisms located in the shared UGT1A-3′UTR region (rs10929303, rs1042640, rs8330) were associated with acetaminophen glucuronidation activity. In addition, the prevalence of rs8330 was significantly lower in patients who had acute liver failure from acetaminophen overdose, suggesting that rs8330 may affect acetaminophen-induced liver injury.
See article at J Pharmacol Exp Ther 2013, 345:297–307.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics