NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids.
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.
Ferguson
Jane F
JF
Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
Phillips
Catherine M
CM
McMonagle
Jolene
J
Pérez-Martínez
Pablo
P
Shaw
Danielle I
DI
Lovegrove
Julie A
JA
Helal
Olfa
O
Defoort
Catherine
C
Gjelstad
Ingrid M F
IM
Drevon
Christian A
CA
Blaak
Ellen E
EE
Saris
Wim H M
WH
Leszczyńska-Gołabek
Iwona
I
Kiec-Wilk
Beata
B
Risérus
Ulf
U
Karlström
Brita
B
Lopez-Miranda
Jose
J
Roche
Helen M
HM
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
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III