Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study.
Michael V Holmes1, Tabassome Simon2, Holly J Exeter3
1Faculty of Population Health Sciences, University College London, London, United Kingdom.
Journal of the American College of Cardiology
|August 7, 2013
Summary
This study found that reducing secretory phospholipase A2-IIA (sPLA2-IIA) mass does not prevent cardiovascular events. Genetic analysis indicates sPLA2-IIA is not a causal factor in major vascular events.
Area of Science:
- Cardiovascular Disease Research
- Genetic Epidemiology
- Biomarker Analysis
Background:
- Elevated secretory phospholipase A2-IIA (sPLA2-IIA) levels correlate with cardiovascular event risk.
- Causality between sPLA2-IIA and cardiovascular events remains unproven.
- Previous sPLA2 inhibitor trials showed no efficacy.
Purpose of the Study:
- To investigate the causal role of sPLA2-IIA in cardiovascular disease.
- To determine if sPLA2-IIA mass or activity causally impacts major vascular events (MVE).
Main Methods:
- Mendelian randomization meta-analysis of 19 general population studies and 10 acute coronary syndrome cohorts.
- Utilized rs11573156 variant in PLA2G2A as a genetic instrumental variable for sPLA2-IIA.
- Analyzed associations between genetic variants, sPLA2-IIA levels, and MVE.
Main Results:
- The rs11573156 C allele significantly reduced sPLA2-IIA mass and activity.
- No significant association was found between the rs11573156 C allele and MVE risk in general populations or ACS cohorts.
- Genetic analysis did not support a causal link between sPLA2-IIA mass/activity and MVE.
Conclusions:
- Reducing sPLA2-IIA mass is unlikely to be an effective therapeutic strategy for cardiovascular event prevention.
- Current evidence does not support sPLA2-IIA as a causal target for cardiovascular disease therapies.
Keywords:
ACSCILDL-CMIMVEMendelian randomizationORRCTSNPacute coronary syndrome(s)cardiovascular diseasesconfidence intervaldrug developmentepidemiologygeneticslow-density lipoprotein cholesterolmajor vascular eventsmyocardial infarctionodds ratiorandomized clinical trialsPLA(2)secretory phospholipase A(2)single-nucleotide polymorphismRelated Concept Videos
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