Abstract 2181: The Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Gene is Associated With Plasma Lp-PLA2 Mass and Activity
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a macrophage derived enzyme that is bound to lipoproteins in plasma. Lp-PLA2 cleaves oxidized phosphatidylcholine into lysophosphatidylcholine (LysoPC) and oxidized non-esterified free fatty acids (oxNEFA). Plasma levels of Lp-PLA2 are associated with cardiovascular disease outcomes. Lp-PLA2 levels are correlated with lipid levels but regulation of Lp-PLA2 levels is not well understood. Sixteen single nucleotide polymorphisms (SNPs) in the Lp-PLA2 gene (PLA2G7) were genotyped using the GoldenGate platform (Illumina) in 995 non-Hispanic Whites from the Coronary Artery Calcification in Type 1 Diabetes Study (CACTI). SNPs were chosen as tagged SNPs or based on position within the gene and flanking regions. Lp-PLA2 mass and activity were determined by the PLAC and the colorimetric activity method (CAM) assays respectively by diaDexus Inc. Principal Component (PC) analyses identified five PCs composed of PLA2G7 SNPs that accounted for 90% of the SNP variation in this population. PC-1 (p<0.0001) and PC-5 (p=0.03) were significantly associated with Lp-PLA2 mass after controlling for age, sex, diabetes, LDL-C, HDL-C, and statin medication use. In addition, PC-5 (p<0.01) was significantly associated Lp-PLA2 activity controlling for the same covariates. Rs12195701 and rs10948300 loaded strongly on PC-1 (factor loading scores of 93 and 92 respectively) and rs17288905 loaded strongly on PC-5 (factor loading score of 83). This study demonstrates the usefulness of Principal Components analyses of multiple SNPs across a gene for determining a gene - phenotype relationship. To our knowledge this is the first report to show an association between multiple SNPs within the PLA2G7 gene and Lp-PLA2 mass and activity. Additional studies are needed to determine the clinical significance of this PLA2G7 genetic variation on the risk of coronary artery disease risk.