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. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.
CITATION STYLE
Al-Hilal, M., AlSaleh, A., Maniou, Z., Lewis, F. J., Hall, W. L., Sanders, T. A. B., & O’Dell, S. D. (2013). Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement. Journal of Lipid Research, 54(2), 542–551. https://doi.org/10.1194/jlr.P032276
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