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http://purl.uniprot.org/citations/24563418http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24563418http://www.w3.org/2000/01/rdf-schema#comment"

Background

Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.

Methods and results

Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20).

Conclusions

This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.org/dc/terms/identifier"doi:10.1161/circgenetics.113.000271"xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Chen L."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Ball S.G."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Altshuler D."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Deloukas P."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Li M."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Li K.W."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Doering A."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Fischer M."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Qu L."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Tang H."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Erdmann J."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Kleber M."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Meitinger T."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Peltonen L."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Wells G.A."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Rice K."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Gabriel S.B."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Rotter J.I."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Schreiber S."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Chen L.'"xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Taylor K.D."xsd:string
http://purl.uniprot.org/citations/24563418http://purl.uniprot.org/core/author"Smith A.J."xsd:string
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