Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement

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 x 10(-19) = P = 4.5 x 10(-18)) and D6D (FADS2) (6.05 x 10(-8) = P = 4.20 x 10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 = P = 2.49 x 10(-16)). The significance of haplotype association with D5D activity (P = 2.19 x 10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 x 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 x 10(-9)) and decreased D6D activity (P = 9.16 x 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).(jlr) 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.-Al-Hilal, M., A. AlSaleh, Z. Maniou, F. J. Lewis, W. L. Hall, T. A. B. Sanders, and S. D. O'Dell on behalf of the MARINA study team. Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement. J. Lipid Res. 2013. 54: 542-551.