Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial

Lipids Health Dis. 2015 Feb 21;14:12. doi: 10.1186/s12944-015-0009-2.


Background: Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation.

Methods: A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels.

Results: The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A.

Conclusion: These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at as NCT01343342.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • Adult
  • Dietary Supplements
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Genetic Association Studies
  • Group II Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / genetics
  • Humans
  • Male
  • Phospholipases A2 / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Triglycerides / blood*


  • Fatty Acids, Omega-3
  • Triglycerides
  • Group II Phospholipases A2
  • Group VI Phospholipases A2
  • PLA2G2A protein, human
  • PLA2G2C protein, human
  • PLA2G2D protein, human
  • PLA2G6 protein, human
  • Phospholipases A2
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human

Associated data