ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-Center Trial to Study Acute Liver Failure in Adults
Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
Who cites it
26 citing papers in PubMed, 61 citations in OpenAlex.
- A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Trial
- The potential of curcumin in mitigating acetaminophen-induced liver damage.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock.BMC anesthesiology · 2023Observational
- Genetic variants associated with ALT elevation from therapeutic acetaminophen.Clinical toxicology (Philadelphia, Pa.) · 2022Article
- CommonJournal of personalized medicine · 2022Article
- The Genomics of Elevated ALT and Adducts in Therapeutic Acetaminophen Treatment: a Pilot Study.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2021Article
- A history of the roles of cytochrome P450 enzymes in the toxicity of drugs.Toxicological research · 2021Review
- Pharmacogenetic Study of Trabectedin-Induced Severe Hepatotoxicity in Patients with Advanced Soft Tissue Sarcoma.Cancers · 2020Article
- Identification of Candidate Risk Factor Genes for Human Idelalisib Toxicity Using a Collaborative Cross Approach.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Effects of the human SULT1A1 polymorphisms on the sulfation of acetaminophen,O-desmethylnaproxen, and tapentadol.Pharmacological reports : PR · 2019Article
- Article
- Biomarkers of drug-induced liver injury: progress and utility in research, medicine, and regulation.Expert review of molecular diagnostics · 2018Review
- Effects of human SULT1A3/SULT1A4 genetic polymorphisms on the sulfation of acetaminophen and opioid drugs by the cytosolic sulfotransferase SULT1A3.Archives of biochemistry and biophysics · 2018Article
- Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective.Toxicology research · 2018Review
- Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature.European journal of clinical pharmacology · 2018Review
- Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.The Journal of pharmacology and experimental therapeutics · 2017Article
- Are Polymorphisms in Genes Relevant to Drug Disposition Predictors of Susceptibility to Drug-Induced Liver Injury?Pharmaceutical research · 2017Review
- Association of Variants of Arginine Vasopressin and Arginine Vasopressin Receptor 1A With Severe Acetaminophen Liver Injury.Cellular and molecular gastroenterology and hepatology · 2017Article
- Editor's Highlight: Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Acetaminophen is a leading cause of acute liver failure (ALF). Genetic differences might predispose some individuals to develop ALF. In this exploratory study, we evaluated genotype frequency differences among patients enrolled by the ALF Study Group who had developed ALF either intentionally from a single-time-point overdose of acetaminophen (n = 78), unintentionally after chronic high doses of acetaminophen (n = 79), or from causes other than acetaminophen (n = 103). The polymorphisms evaluated included those in genes encoding putative acetaminophen-metabolizing enzymes (UGT1A1, UGT1A6, UGT1A9, UGT2B15, SULT1A1, CYP2E1, and CYP3A5) as well as CD44 and BHMT1. Individuals carrying the CYP3A5 rs776746 A allele were overrepresented among ALF patients who had intentionally overdosed with acetaminophen, with an odds ratio of 2.3 (95% confidence interval, 1.1-4.9; P = 0.034) compared with all other ALF patients. This finding is consistent with the enhanced bioactivation of acetaminophen by the CYP3A5 enzyme. Persons homozygous for the CD44 rs1467558 A allele were also overrepresented among patients who had unintentionally developed ALF from chronic acetaminophen use, with an odds ratio of 4.0 (1.0-17.2, P = 0.045) compared with all other ALF subjects. This finding confirms a prior study that found elevated serum liver enzyme levels in healthy volunteers with the CD44 rs1467558 AA genotype who had consumed high doses of acetaminophen for up to 2 weeks. However, both genetic associations were considered relatively weak, and they were not statistically significant after adjustment for multiple comparisons testing. Nevertheless, both CYP3A5 rs776746 and CD44 rs1467558 warrant further investigation as potential genomic markers of enhanced risk of acetaminophen-induced ALF.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.