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

J Cardiovasc Med (Hagerstown). 2015 Jan;16(1):29-36. doi: 10.2459/JCM.0000000000000057.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics*
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
  • Aged
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / genetics*
  • Female
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Propensity Score
  • Proportional Hazards Models
  • Prospective Studies

Substances

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human