Lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms and cardiovascular events in patients with coronary artery disease.

AIMS: We tested the hypothesis that variations in the PLA2G7 gene encoding the lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme deemed to have proatherogenic activity, affect the Lp-PLA2 levels and predicts cardiovascular events. METHODS: Using a prospective cohort study design, we investigated incident cardiovascular events as a function of the PLA2G7 gene for rs1805017, rs1805018, and rs1051931 single-nucleotide polymorphisms (SNPs) in 643 randomly selected white patients from the GENICA Study, who at baseline underwent coronary angiography, measurement of Lp-PLA2 mass and activity. Cardiovascular event-free survival was compared across the genotypes by Cox regression, propensity score matching, and haplotype analysis. RESULTS: The rs1805018 SNP did not follow the Hardy-Weinberg equilibrium and was not further explored. The rs1805017 GG genotype had a lower Lp-PLA2 mass and a higher Lp-PLA2 activity, thus suggesting that this SNP is functional. Long-term follow-up (median 7.8 years) was obtained in 75% of the cohort and allowed recording of incident cardiovascular events in 25.8% of the patients. On Cox regression analysis, the common rs1805017 GG genotype predicted acute myocardial infarction (AMI) [hazard ratio 1.75, 95% confidence interval (CI) 1.03-2.99, P = 0.041]; this finding was confirmed on propensity score matching (82.6% AMI-free survival in GG vs. 94.4% in GA + AA, P = 0.003). The rs1805017 and rs1051931 G/G haplotype was also associated with AMI (52.7 vs. 42.2%, P = 0.026) and cardiovascular event incidence (49.5 vs. 41.7%, P = 0.025). CONCLUSION: In high-risk coronary artery disease patients of European ancestry, the PLA2G7 rs1805017 GG genotype is associated with increased Lp-PLA2 plasma activity and AMI.