title: Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study.
abstract: BACKGROUND
  The delta-5 and delta-6 desaturases, encoded by the FADS1 and FADS2 genes, are rate-limiting enzymes in polyunsaturated fatty acid (PUFA) biosynthesis. Single nucleotide polymorphisms in the FADS gene cluster region have been associated with both PUFA concentrations in plasma or erythrocyte membrane phospholipids and cholesterol concentrations in recent genome-wide association studies.
  
  
  OBJECTIVE
  We examined whether genetic variations in the FADS gene cluster region interact with dietary intakes of n-3 (omega-3) and n-6 (omega-6) PUFAs to affect plasma total, HDL-, and non-HDL-cholesterol concentrations.
  
  
  METHODS
  Dietary intakes of n-3 and n-6 PUFAs, plasma concentrations of total and HDL cholesterol, and rs174546, rs482548, and rs174570 in the FADS gene cluster region were measured in 3575 subjects in the second survey of the Doetinchem Cohort Study.
  
  
  RESULTS
  Significant associations between rs174546 genotypes and total and non-HDL-cholesterol concentrations were observed in the group with a high intake of n-3 PUFAs (> or =0.51% of total energy; P = 0.006 and 0.047, respectively) but not in the low-intake group (P for interaction = 0.32 and 0.51, respectively). The C allele was associated with high total and non-HDL-cholesterol concentrations. Furthermore, the C allele was significantly associated with high HDL-cholesterol concentrations in the group with a high intake of n-6 PUFAs (> or =5.26% of total energy, P = 0.004) but not in the group with a low intake (P for interaction = 0.02).
  
  
  CONCLUSIONS
  Genetic variation in the FADS1 gene potentially interacts with dietary PUFA intakes to affect plasma cholesterol concentrations, which should be investigated further in other studies.
authors.affiliation: Division of Human Nutrition, Wageningen University Research Center, Wageningen, Netherlands. kevin.lu@wur.nl
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Lu
authors.forename: Edith Jm
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Martijn Et
authors.initials: ME
authors.lastname: Dollé
authors.forename: Sandra
authors.initials: S
authors.lastname: Imholz
authors.forename: Wm Monique
authors.initials: WM
authors.lastname: Verschuren
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Jolanda Ma
authors.initials: JM
authors.lastname: Boer
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D000090943:Delta-5 Fatty Acid Desaturase; D002784:Cholesterol; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human