title: NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids.
abstract: OBJECTIVE
  Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS).
  
  
  METHODS
  Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions.
  
  
  RESULTS
  Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC+AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes.
  
  
  CONCLUSIONS
  Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.
authors.affiliation: Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phillips
authors.forename: Jolene
authors.initials: J
authors.lastname: McMonagle
authors.forename: Pablo
authors.initials: P
authors.lastname: Pérez-Martínez
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Shaw
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Ingrid M F
authors.initials: IM
authors.lastname: Gjelstad
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Iwona
authors.initials: I
authors.lastname: Leszczyńska-Gołabek
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Brita
authors.initials: B
authors.lastname: Karlström
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000368:Aged; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III