PT  - JOURNAL ARTICLE
AU  - Heruth, Daniel P.
AU  - Shortt, Katherine
AU  - Zhang, Nini
AU  - Li, Ding-You
AU  - Zhang, Li Q.
AU  - Qing Ye, Shui
TI  - Genetic Association of Single Nucleotide Polymorphisms with Acetaminophen-Induced Hepatotoxicity
AID  - 10.1124/jpet.118.248583
DP  - 2018 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 95--100
VI  - 367
IP  - 1
4099  - http://jpet.aspetjournals.org/content/367/1/95.short
4100  - http://jpet.aspetjournals.org/content/367/1/95.full
SO  - J Pharmacol Exp Ther2018 Oct 01; 367
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.