ArticleClinical toxicology (Philadelphia, Pa.)2022
Genetic variants associated with ALT elevation from therapeutic acetaminophen.
Article in Clinical toxicology (Philadelphia, Pa.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 10 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
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSeveral studies have suggested genetic variants associated with acetaminophen induced liver injury (DILI) following overdose. Genetic variation associated with acetaminophen-induced alanine aminotransferase elevation during therapeutic dosing has not been examined.
methodsWe performed genetic analyses on patients that ingested therapeutic doses of 4 grams of acetaminophen for up to 16 days. We examined 20 genes previously implicated in the metabolism of acetaminophen or the development of immune-mediated DILI using the Illumina Multi-Ethnic Global Array 2. Autosomes were aligned and imputed using TOPMed. A candidate gene region analysis was performed by testing each gene individually using linkage disequilibrium (LD) pruned variants with the adaptive sum of powered scores (aSPU) test from the aSPU R package. The highest measured ALT during therapy, the maximum ALT, was used as the outcome.
results192 subjects taking therapeutic APAP were included in the genetic analysis. 136 (70.8%) were female, 133 (69.2%) were Caucasian race, and the median age was 34 years (IQR: 26, 46). Age > 50 years was the only clinical factor associated with maximum ALT increase. Variants in
conclusionAcetaminophen induced ALT elevation at therapeutic doses was not associated with variation in most genes associated with acetaminophen metabolism or immune-induced DILI in this cohort. The role of
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