TY - JOUR
T1 - Association of Variants of Arginine Vasopressin and Arginine Vasopressin Receptor 1A With Severe Acetaminophen Liver Injury
AU - Randesi, Matthew
AU - Levran, Orna
AU - Correa da Rosa, Joel
AU - Hankins, Julia
AU - Rule, Jody
AU - Kreek, Mary Jeanne
AU - Lee, William M.
AU - Reuben, Adrian
AU - Fontana, Robert J.
AU - Davern, Timothy
AU - McGuire, Brendan
AU - Stravitz, R. Todd
AU - Durkalski, Valerie
AU - Liou, Iris
AU - Fix, Oren
AU - Schilsky, Michael
AU - Ganger, Daniel
AU - Chung, Raymond T.
AU - Koch, David
AU - Reddy, K. Rajender
AU - Rossaro, Lorenzo
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - Impulsivity
KW - Overdose
KW - Pituitary-Adrenal Axis
KW - Stress Responsivity
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U2 - 10.1016/j.jcmgh.2017.01.008
DO - 10.1016/j.jcmgh.2017.01.008
M3 - Article
C2 - 28462386
AN - SCOPUS:85018250021
SN - 2352-345X
VL - 3
SP - 500
EP - 505
JO - CMGH
JF - CMGH
IS - 3
ER -