Gene variations of nitric oxide synthase regulate the effects of a saturated fat rich meal on endothelial function.
OBJECTIVE
Endothelial nitric oxide synthase (eNOS) gene variations have been linked to a higher risk for cardiovascular diseases (CVD) by unknown mechanisms. Our aim was to determine if two single nucleotide polymorphisms (SNPs) located in NOS3 (E298D and i19342) interfere with microvascular endothelial function (MEF) and/or oxidative stress during the postprandial state.


METHODS
MEF was assessed with laser Doppler flowmetry at baseline and 2, 4, 6 and 8 h after ingestion of a single fatty meal (60% fat, 15% proteins and 25% carbohydrates) by 40 healthy young males. Oxidative stress was measured by nitrites/nitrates and oxidized LDL (LDL-ox) concentrations in fasting and postprandial states.


RESULTS
Postprandial MEF was impaired in the carriers of minor alleles of the SNPs (global mean 60.99% Vs 87.25%, p = 0.016 for i19342; 63.62% Vs 95.71%, p = 0.011 for E298D). Carriers of E298D showed a higher LDL-ox at fasting and postprandial measures, and lower nitrites/nitrates at fasting.


CONCLUSIONS
Minor allele carriers for E298D and i19342 have an impaired postprandial MEF and increased oxidative stress. Our results both provide insight into the higher risk of CVD attributed to E298D and identify variants that affect MEF in a healthy population.
Delgado-Lista
Javier
J
Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital, University of Cordoba and CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III. 14004, Cordoba, Spain.
Garcia-Rios
Antonio
A
Perez-Martinez
Pablo
P
Fuentes
Francisco
F
Jiménez-Gomez
Yolanda
Y
Gomez-Luna
Maria Jose
MJ
Parnell
Laurence D
LD
Marin
Carmen
C
Lai
Chao Qiang
CQ
Perez-Jimenez
Francisco
F
Ordovas
Jose Maria
JM
Lopez-Miranda
Jose
J
D000483:Alleles; D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics; D008078:Cholesterol, LDL / Q000032:analysis; D004727:Endothelium / Q000201:enzymology*; D005227:Fatty Acids / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D012307:Risk Factors; D044465:White People
D008078:Cholesterol, LDL; D005227:Fatty Acids; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III