Association of Variants of Arginine Vasopressin and Arginine Vasopressin Receptor 1A With Severe Acetaminophen Liver Injury

Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M. Lee*, Adrian Reuben, Robert J. Fontana, Timothy Davern, Brendan McGuire, R. Todd Stravitz, Valerie Durkalski, Iris Liou, Oren Fix, Michael Schilsky, Daniel Ganger, Raymond T. Chung, David Koch, K. Rajender ReddyLorenzo Rossaro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background & Aims Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. Methods We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress. Study subjects were 229 white patients admitted to tertiary care liver centers for ALF that was determined to be due to acetaminophen toxicity after careful review of historical and biochemical data. Identification of relevant SNPs used Sanger sequencing, TaqMan, or custom microarray. Association tests were carried out to compare genotype frequencies between patients and healthy white controls. Results The mean age was 37 years, and 75.6% were female, with similar numbers classified as intentional overdose or unintentional (without suicidal intent, occurring for a period of several days, usually due to pain). There was concomitant alcohol abuse in 30%, opioid use in 33.6%, and use of other drugs of abuse in 30.6%. The genotype frequencies of 2 SNPs were found to be significantly different between the cases and controls, specifically SNP rs2282018 in the arginine vasopressin gene (AVP, odds ratio 1.64) and SNP rs11174811 in the AVP receptor 1A gene (AVPR1A, odds ratio 1.89), both of which have been previously linked to a drug use disorder diagnosis. Conclusions Patients who develop acetaminophen-related ALF have increased frequency of gene variants that may cause altered stress responsivity, which has been shown to be associated with other unrelated substance use disorders.

Original languageEnglish (US)
Pages (from-to)500-505
Number of pages6
Issue number3
StatePublished - May 2017


  • Impulsivity
  • Overdose
  • Pituitary-Adrenal Axis
  • Stress Responsivity

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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