PLA2G10 Gene Variants, sPLA2 Activity, and Coronary Heart Disease Risk.

BACKGROUND Observational studies report that secretory phospholipase A2 (sPLA2) activity is a marker for coronary heart disease (CHD) risk, and activity measures are thought to represent the composite activity of sPLA2-IIA, -V, and -X. The aim of this study was to use genetic variants of PLA2G10, encoding sPLA2-X, to investigate the contribution of sPLA2-X to the measure of sPLA2 activity and coronary heart disease (CHD) risk traits and outcome. METHODS AND RESULTS Three PLA2G10 tagging single-nucleotide polymorphisms (rs72546339, rs72546340, and rs4003232) and a previously studied PLA2G10 coding single-nucleotide polymorphism rs4003228, R38C, were genotyped in a nested case: control cohort drawn from the prospective EPIC-Norfolk Study (2175 cases and 2175 controls). Meta-analysis of rs4003228 (R38C) and CHD was performed using data from the Northwick Park Heart Study II and 2 published cohorts AtheroGene and SIPLAC, providing in total an additional 1884 cases and 3119 controls. EPIC-Norfolk subjects in the highest tertile of sPLA2 activity were older and had higher inflammatory markers compared with those in the lowest tertile for sPLA2 activity. None of the PLA2G10 tagging single-nucleotide polymorphism nor R38C, a functional variant, were significantly associated with sPLA2 activity, intermediate CHD risk traits, or CHD risk. In meta-analysis, the summary odds ratio for R38C was odds ratio=0.97 (95% confidence interval, 0.77-1.22). CONCLUSIONS PLA2G10 variants are not significantly associated with plasma sPLA2 activity or with CHD risk.