title: Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios.
abstract: Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean +/- SD age: 14.7 +/- 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 <or= P <or= 6.1E-5), lower C20:4n-6 levels (7.1E-69 <or= P <or= 1.2E-12), and lower D5D activity (7.2E-44 <or= P <or= 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents.
authors.affiliation: Inserm U744, Institut Pasteur de Lille, Univ Lille Nord de France, UDSL, 59019 Lille, France.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Bokor
authors.forename: Julie
authors.initials: J
authors.lastname: Dumont
authors.forename: Andre
authors.initials: A
authors.lastname: Spinneker
authors.forename: Marcela
authors.initials: M
authors.lastname: Gonzalez-Gross
authors.forename: Esther
authors.initials: E
authors.lastname: Nova
authors.forename: Kurt
authors.initials: K
authors.lastname: Widhalm
authors.forename: George
authors.initials: G
authors.lastname: Moschonis
authors.forename: Peter
authors.initials: P
authors.lastname: Stehle
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Henauw
authors.forename: Dènes
authors.initials: D
authors.lastname: Molnàr
authors.forename: Luis A
authors.initials: LA
authors.lastname: Moreno
authors.forename: Aline
authors.initials: A
authors.lastname: Meirhaeghe
authors.forename: Jean
authors.initials: J
authors.lastname: Dallongeville
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood* / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000737:chemistry; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human