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RESEARCH PRODUCT

A029 Identification of polymorphisms in the gene encoding secreted phospholipase A2 group X and study of their role in coronary artery disease. The atherogene study

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Human secreted phospholipases A2 (sPLA2s) represent novel attractive therapeutic targets and biomarkers in coronary artery diseases (CAD). We have shown that human Group X sPLA2 (hGX sPLA2) is present in atherosclerotic lesions and that hGX sPLA2 modified LDL induces foam cell formation. To elucidate whether hGX sPLA2 has a causative role in CAD we have screened the human PLA2G10 gene to identify frequent polymorphisms, and we have examined their possible association with cardiovascular end-points and intermediate inflammatory phenotypes in a large prospective study of patients with CAD (the AtheroGene study). Although no significant association was found between the various polymorphisms identified and lipids or inflammatory markers, patients carriers of the C allele of the T-512C polymorphism located in the 5’ untranslated region showed a decreased risk of recurrent cardiovascular events. Molecular analysis of the only missense variant (R38C) showed its functional relevance as it leads to a profound change in expression and secretion of hGX sPLA2.