Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.
- 1Faculté de pharmacie, Université de Montréal, Montreal, QC, Canada.
- 2Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, QC, Canada.
- 3Montreal Heart Institute, Montreal, QC, Canada.
Abstract
Arachidonate 5-lipoxygenase (5-LO) and its activating protein, encoded by ALOX5 and ALOX5AP respectively, are two leukotriene pathway proteins suspected to play a role in atherosclerotic cardiovascular disease (ASCVD) through inflammatory mechanisms. Prior genetic association studies linking ALOX5 and ALOX5AP to ASCVD have motivated clinical trials of 5-LO inhibitors, such as atreleuton, which was associated with reduced atherosclerotic plaque progression in patients with a recent acute coronary syndrome in a phase II trial. However, the effect of 5-LO inhibition on ASCVD clinical outcomes remains unclear. Using data from the UK Biobank, we revisit previously reported genetic associations of ALOX5 and ALOX5AP with ASCVD using a multi-ancestry meta-analysis including data from 378,962 participants. We characterize ancestral differences in previously studied ALOX5 and ALOX5AP polymorphisms which could have led to population stratification. When adequately accounting for ancestry, these previous associations were not replicated. In addition to our replication efforts, we used association scans and transcriptome-wide association studies to test the involvement of leukotriene pathway genes with ASCVD. Overall, our results do not support a role for genetic variation in ALOX5 or its activating protein in ASCVD risk.
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BibTeX
@article{stlaurent2026revisiting,
title = {{Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.}},
author = {Tristan St-Laurent and Julien St-Pierre and Julien Quang Le Van and Marc-André Legault},
journal = {Frontiers in genetics},
year = {2026},
month = oct,
doi = {10.3389/fgene.2026.1812905},
url = {https://europepmc.org/article/MED/42948828},
note = {CC BY},
}
RIS
TY - JOUR
TI - Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.
AU - Tristan St-Laurent
AU - Julien St-Pierre
AU - Julien Quang Le Van
AU - Marc-André Legault
PY - 2026
DA - 2026/10/14
JO - Frontiers in genetics
DO - 10.3389/fgene.2026.1812905
UR - https://europepmc.org/article/MED/42948828
AB - Arachidonate 5-lipoxygenase (5-LO) and its activating protein, encoded by ALOX5 and ALOX5AP respectively, are two leukotriene pathway proteins suspected to play a role in atherosclerotic cardiovascular disease (ASCVD) through inflammatory mechanisms. Prior genetic association studies linking ALOX5 and ALOX5AP to ASCVD have motivated clinical trials of 5-LO inhibitors, such as atreleuton, which was associated with reduced atherosclerotic plaque progression in patients with a recent acute coronary syndrome in a phase II trial. However, the effect of 5-LO inhibition on ASCVD clinical outcomes remains unclear. Using data from the UK Biobank, we revisit previously reported genetic associations of ALOX5 and ALOX5AP with ASCVD using a multi-ancestry meta-analysis including data from 378,962 participants. We characterize ancestral differences in previously studied ALOX5 and ALOX5AP polymorphisms which could have led to population stratification. When adequately accounting for ancestry, these previous associations were not replicated. In addition to our replication efforts, we used association scans and transcriptome-wide association studies to test the involvement of leukotriene pathway genes with ASCVD. Overall, our results do not support a role for genetic variation in ALOX5 or its activating protein in ASCVD risk.
SN - 1664-8021
ER -