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Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.
Frontiers in Genetics · · Journal Article · Open access
St-Laurent, St-Pierre + more
Abstract ↗AI summary
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In a multi-ancestry meta-analysis of 378,962 UK Biobank participants, genetic variation in ALOX5 and ALOX5AP is not supported as a driver of ASCVD risk after ancestry is properly accounted for.
- Why it matters: Prior genetic links to leukotriene pathway targets motivated 5-LO inhibitor trials, but whether these variants translate into ASCVD clinical outcomes has remained uncertain.
- What they did: The study reanalyzed reported ALOX5 and ALOX5AP associations in UK Biobank using multi-ancestry meta-analysis, ancestry stratification checks, plus association scans and transcriptome-wide association studies.
- The result: After adequate adjustment for ancestry, earlier associations were not replicated, and the overall findings do not support a role for genetic variation in ALOX5 or ALOX5AP in ASCVD risk.
The findingWhy it mattersWhat they didThe result
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