RT Journal Article
SR Electronic
T1 Genetic Association of Single Nucleotide Polymorphisms with Acetaminophen-Induced Hepatotoxicity
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 95
OP 100
DO 10.1124/jpet.118.248583
VO 367
IS 1
A1 Daniel P. Heruth
A1 Katherine Shortt
A1 Nini Zhang
A1 Ding-You Li
A1 Li Q. Zhang
A1 Shui Qing Ye
YR 2018
UL http://jpet.aspetjournals.org/content/367/1/95.abstract
AB Acetaminophen is commonly used to reduce pain and fever. Unfortunately, overdose of acetaminophen is a leading cause of acute liver injury and failure in many developed countries. The majority of acetaminophen is safely metabolized in the liver and excreted in the urine; however, a small percentage is converted to the highly reactive N-acetyl-p-benzoquinone imine (NAPQI). At therapeutic doses, NAPQI is inactivated by glutathione S-transferases, but at toxic levels, excess NAPQI forms reactive protein adducts that lead to hepatotoxicity. Individual variability in the response to both therapeutic and toxic levels of acetaminophen suggests a genetic component is involved in acetaminophen metabolism. In this review, we evaluate the genetic association studies that have identified 147 single nucleotide polymorphisms linked to acetaminophen-induced hepatotoxicity. The identification of novel genetic markers for acetaminophen-induced hepatotoxicity provides a rich resource for further evaluation and may lead to improved prognosis, prevention, and treatment.