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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 A 2  (PLA 2 ) 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 PLA 2  genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.

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