Abstract
Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-PUFAs and desaturase activities estimated in plasma and erythrocytes. Minor allele carriage associated with decreased activities of D5D (FADS1) (5.84 × 10(-19) ≤ P ≤ 4.5 × 10(-18)) and D6D (FADS2) (6.05 × 10(-8) ≤ P ≤ 4.20 × 10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤ P ≤ 2.49 × 10(-16)). The significance of haplotype association with D5D activity (P = 2.19 × 10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 × 10(-28)) was much stronger. In a randomized controlled dietary intervention, increasing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) intake significantly increased D5D (P = 4.0 × 10(-9)) and decreased D6D activity (P = 9.16 × 10(-6)) after doses of 0.45, 0.9, and 1.8 g/day for six months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2 locus appear to influence D5D and D6D activity, and rs174537 genotype interacts with dietary EPA+DHA to modulate D5D.
Highlights
Delta-5 and delta-6 desaturases (D5D and Delta-6 desaturase (D6D)) are key enzymes in endogenous synthesis of long-chain PUFAs
There was no significant interaction between any of the single nucleotide polymorphisms (SNP) genotypes and treatment in determining D6D activity. In this sample of healthy subjects, we have shown that genotypes of three SNPs in the FADS1-FADS2 gene cluster were strongly associated with proportions of Long-chain polyunsaturated fatty acids PUFA (LC-PUFA) and desaturase activities estimated in plasma and erythrocytes
Minor allele carriage associated with decreased activity of Delta-5 desaturase (D5D) (FADS1) and D6D (FADS2) was reflected in increased proportions of substrates and decreased products in n-6 and n-3 LC-PUFA synthetic pathways
Summary
The MARINA Study The MARINA (modulation of atherosclerosis risk by increasing doses of N-3 fatty acids) trial was a single-center dietary intervention study of randomized double-blind parallel design to test the effects of three daily doses of DHA and EPA on endothelial function and established cardiovascular disease risk factors [23]. Written, informed consent was given by participants, who were healthy nonsmoking men and women between 45 and 70 years of age, recruited through media advertisements and screened as described previously [23]. During an initial run-in period of four weeks, participants took olive oil (BP specification) placebo capsules while restricting oily fish intake, after which baseline measurements of outcome variables were made. The dietary intervention phase involved supplementation with encapsulated EPA and DHA at three doses (0.45, 0.9, and 1.8 g/day), compared with placebo. Compliance was determined by assessing the DHA and EPA content in erythrocyte phosphoglycerides at baseline, 6 months, and 12 months. The oil blends were supplied by Croda Chemicals Europe Ltd. Quality control analysis was performed by Croda Chemicals Europe Ltd
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