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Genetic variants associated with ALT elevation from therapeutic acetaminophen
Andrew A Monte1,2,3,4, Ian Arriaga Mackenzie5, Jack Pattee5
1Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Clinical Toxicology (Philadelphia, Pa.)
|September 14, 2022
Summary
Genetic variants in SULT1E1 may influence alanine aminotransferase (ALT) elevation during acetaminophen therapy. Further research is needed to explore SULT1E1
Area of Science:
- Pharmacogenomics
- Hepatology
- Genetic Epidemiology
Background:
- Genetic variants are linked to acetaminophen-induced liver injury (DILI) after overdose.
- No prior studies examined genetic variation related to alanine aminotransferase (ALT) elevation during therapeutic acetaminophen dosing.
Purpose of the Study:
- To investigate the association between genetic variation and ALT elevation in individuals taking therapeutic doses of acetaminophen.
- To identify specific genes influencing acetaminophen metabolism and immune-mediated DILI.
Main Methods:
- Genetic analysis of 192 subjects receiving therapeutic acetaminophen doses (up to 4 grams/day for 16 days).
- Examined 20 candidate genes using Illumina Multi-Ethnic Global Array, with imputation via TOPMed.
- Candidate gene region analysis employed the adaptive sum of powered scores (aSPU) test.
Main Results:
- Age over 50 was the only clinical factor associated with maximum ALT increase.
- Genetic variants within the SULT1E1 gene (Sulfotransferase Family 1E Member 1) were associated with maximum ALT.
- The association with SULT1E1 was attributed to the cumulative effects of multiple variants, not a single one.
Conclusions:
- Acetaminophen-induced ALT elevation at therapeutic doses is not strongly associated with variants in most studied genes.
- The role of SULT1E1 gene polymorphisms in acetaminophen-induced ALT elevation warrants further investigation.
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