The association of PLA2G2A single nucleotide polymorphisms with type IIa secretory phospholipase A2 level but not its activity in patients with stable coronary heart disease

Gene. 2015 Jun 10;564(1):29-34. doi: 10.1016/j.gene.2015.03.030. Epub 2015 Mar 17.

Abstract

Background: Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene (PLA2G2A) affect sPLA2-IIa level and activity in patients with diabetes mellitus, acute coronary syndrome or recent cardiovascular surgical interventions. Our study examined the effects of PLA2G2A SNPs on sPLA2-IIa levels and activity in patients with stable CHD.

Methods and results: The study included a total of 396 patients (30% women). Six SNPs of PLA2G2A: rs1774131, rs11573156, rs3753827, rs2236771, rs876018, and rs3767221, sPLA2-IIa level and activity were determined for all patients. Four SNPs (rs1774131, rs11573156, rs3753827, rs3767221) correlated with sPLA2-IIa level but not activity with the strongest correlation observed for rs11573156 (r=0.49, p=3.7·10(-13)). All partial correlations controlling for rs11573156 became insignificant, whereas, the partial correlation of rs11573156 with sPLA2-IIa level controlling for other SNPs remained significant. Only rs11573156 showed association with sPLA2-IIa level in multiple regression analysis. Haplotype CGGGTT was associated with a significantly higher sPLA2-IIa level but not activity compared with all other haplotypes after adjustment for gender, age, diabetes mellitus and statin use (p=0.0023).

Conclusions: According to our results the examined SNPs affect the sPLA2-IIa level to a greater extent than its activity in patients with stable CHD. It seems that, the impact of these SNPs on sPLA2-IIa level is caused by their linkage to rs11573156 whose minor alleles were associated with higher sPLA2-IIa level. At the same time haplotype CGGGTT, which includes the minor allele of rs11573156, was the dominant haplotype and was associated with the highest sPLA2-IIa level.

Keywords: Polymorphisms of PLA2G2A; Stable CHD; sPLA2-IIA activity; sPLA2-IIA level.

MeSH terms

  • Aged
  • Coronary Disease / blood
  • Coronary Disease / enzymology
  • Coronary Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Group II Phospholipases A2 / blood*
  • Group II Phospholipases A2 / genetics*
  • Haplotypes
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Group II Phospholipases A2
  • PLA2G2A protein, human