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

TY - JOUR

T1 - Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement

AU - Al Hilal, Maryam

AU - Alsaleh, Aseel

AU - Maniou, Zoitsa

AU - Lewis, Fiona J

AU - Hall, Wendy L

AU - Sanders, Thomas A B

AU - O'Dell, Sandra D

PY - 2013/2

Y1 - 2013/2

N2 - 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 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) (5.84x10(-19) ≤P≤ 4.5x10(-18)) and D6D (FADS2) (6.05x10(-8) ≤P≤ 4.20x10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤P≤ 2.49x10(-16)). The significance of SNP haplotype association with D5D activity (P = 2.19x10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39x10(-28)) was much stronger. In a randomised controlled dietary intervention, increasing EPA (20:5n-3) and DHA (22:6n-3) intake significantly increased D5D (P = 4.0x10(-9)) and decreased D6D activity (P = 9.16x10(-6)) after doses of 0.45, 0.9 and 1.8 g/day for 6 months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity (P = 0.05 in plasma; P = 0.02 in erythrocytes). 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.

AB - 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 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) (5.84x10(-19) ≤P≤ 4.5x10(-18)) and D6D (FADS2) (6.05x10(-8) ≤P≤ 4.20x10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤P≤ 2.49x10(-16)). The significance of SNP haplotype association with D5D activity (P = 2.19x10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39x10(-28)) was much stronger. In a randomised controlled dietary intervention, increasing EPA (20:5n-3) and DHA (22:6n-3) intake significantly increased D5D (P = 4.0x10(-9)) and decreased D6D activity (P = 9.16x10(-6)) after doses of 0.45, 0.9 and 1.8 g/day for 6 months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity (P = 0.05 in plasma; P = 0.02 in erythrocytes). 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.

U2 - 10.1194/jlr.P032276

DO - 10.1194/jlr.P032276

M3 - Article

C2 - 23160180

SN - 0022-2275

VL - 54

SP - 542

EP - 551

JO - Journal of Lipid Research

JF - Journal of Lipid Research

IS - 2

ER -