title: Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement.
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.
authors.affiliation: Diabetes and Nutritional Sciences Division,  School of Medicine, Kingrsquos College London, London SE1 9NH,  United Kingdom.
authors.forename: Maryam
authors.initials: M
authors.lastname: Al-Hilal
authors.forename: Aseel
authors.initials: A
authors.lastname: Alsaleh
authors.forename: Zoitsa
authors.initials: Z
authors.lastname: Maniou
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Lewis
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Hall
authors.forename: Thomas A B
authors.initials: TA
authors.lastname: Sanders
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D000090943:Delta-5 Fatty Acid Desaturase; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000097:blood* / Q000737:chemistry*; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D005787:Gene Frequency / Q000187:drug effects / Q000235:genetics; D056426:Genetic Loci / Q000187:drug effects / Q000235:genetics*; D006239:Haplotypes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human