TY - JOUR T1 - Genetic Association of Single Nucleotide Polymorphisms with Acetaminophen-Induced Hepatotoxicity JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 95 LP - 100 DO - 10.1124/jpet.118.248583 VL - 367 IS - 1 AU - Daniel P. Heruth AU - Katherine Shortt AU - Nini Zhang AU - Ding-You Li AU - Li Q. Zhang AU - Shui Qing Ye Y1 - 2018/10/01 UR - http://jpet.aspetjournals.org/content/367/1/95.abstract N2 - 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. ER -