Abstract 4111: Genetic Variants within the PLA2G2A Gene Encoding Secretory Phospholipase A2 Group IIA are Related to the Risk of Myocardial Infarction
Introduction: Secretory phospholipase A2 (sPLA2) hydrolyze the sn-2 ester bond of phospholipids and lipoproteins. sPLA2 has been implicated in coronary artery disease (CAD): treatment with sPLA2 modifies LDL lipoproteins towards a higher affinity for extracellular matrix proteins, resulting in an increased retention of LDL particles in the arterial wall, an early hallmark of atherosclerotic lesion progression. The sPLA2-mediated hydrolysis of phospholipids yields known precursors of proinflammatory mediators, and lipoproteins that are more susceptible to lipid peroxidation generating more bioactive phospholipids. In addition, high sPLA2 levels increase the risk for future coronary events in CAD patients and in apparently healthy individuals. Moreover, the gene encoding sPLA2, PLA2G2A, is localized on chr1p36, a genomic region that has been linked to myocardial infarction (MI). Thus, we hypothesized that genetic variants within the PLA2G2A are associated with an increased risk for MI.
Methods: 7 SNPs covering the gene region were genotyped in index MI patients (n=1,429 Caucasians) from the German MI family study and in an age and sex stratified sample of healthy individuals from the general population (MONICA study Augsburg, DNA of 1,419 Caucasians). Additionally, 607 incident MI cases from the KORA Augsburg MI registry were genotyped to verify the findings.
Results: Linkage disequilibrium analysis revealed a block consisting of 3 SNP markers. We found association of the minor alleles (all with minor allele frequency >10%) of these SNPs with MI using Armitage’s trend test (best SNP OR(men)= 1.47[1.18–1.83]; OR(women)= 1.32[0.97–1.78]). The significance remained when performing 50.000 permutations to test for emipirical significance. Multivariate adjustments revealed consistent results. We were able to confirm these results using the KORA MI registry cases: OR(men)= 1.39[1.08–1.78], OR(women)= 1.32[0.97–1.78].
Conclusions: These data suggest that common genetic variants in PLA2G2A gene region are associated with susceptibility to MI. These results corroborate the role of sPLA2 in the pathogenesis of CAD.