Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy (D.P.H., K.S., N.Z., L.Q.Z., S.Q.Y.), Division of Gastroenterology, Department of Pediatrics, Children's Mercy (N.Z., D.-Y.L.), and Department of Biomedical and Health Informatics (K.S., S.Q.Y.), University of Missouri Kansas City School of Medicine, Kansas City, Missouri; Division of Cell Biology and Biophysics, University of Missouri Kansas City School of Biological Sciences, Kansas City, Missouri (K.S.); and Department of Pediatrics, Tangdu Hospital, The Fourth Military Medical University, Xian, China (N.Z.)
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy (D.P.H., K.S., N.Z., L.Q.Z., S.Q.Y.), Division of Gastroenterology, Department of Pediatrics, Children's Mercy (N.Z., D.-Y.L.), and Department of Biomedical and Health Informatics (K.S., S.Q.Y.), University of Missouri Kansas City School of Medicine, Kansas City, Missouri; Division of Cell Biology and Biophysics, University of Missouri Kansas City School of Biological Sciences, Kansas City, Missouri (K.S.); and Department of Pediatrics, Tangdu Hospital, The Fourth Military Medical University, Xian, China (N.Z.).
J Pharmacol Exp Ther. 2018 Oct;367(1):95-100. doi: 10.1124/jpet.118.248583. Epub 2018 Aug 3.
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 -acetyl--benzoquinone imine (NAPQI). At therapeutic doses, NAPQI is inactivated by glutathione -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.
对乙酰氨基酚通常用于缓解疼痛和退烧。不幸的是，在许多发达国家，对乙酰氨基酚过量是导致急性肝损伤和衰竭的主要原因。大多数对乙酰氨基酚在肝脏中安全代谢并从尿液中排出；然而，一小部分转化为高度反应性的 -乙酰--苯醌亚胺 (NAPQI)。在治疗剂量下，NAPQI 被谷胱甘肽转移酶失活，但在毒性水平下，过量的 NAPQI 形成反应性蛋白质加合物，导致肝毒性。对乙酰氨基酚的治疗和毒性水平的反应个体差异表明遗传因素参与了对乙酰氨基酚的代谢。在这篇综述中，我们评估了已确定与对乙酰氨基酚引起的肝毒性相关的 147 个单核苷酸多态性的遗传关联研究。对乙酰氨基酚诱导的肝毒性的新型遗传标志物的鉴定为进一步评估提供了丰富的资源，并可能导致改善预后、预防和治疗。
