The Glu298Asp single nucleotide polymorphism in the endothelial nitric oxide synthase gene differentially affects the vascular response to acute consumption of fruit and vegetable puree based drinks.
METHODS
Diets low in fruits and vegetables (FV) are responsible for 2.7 million deaths from cardiovascular diseases (CVD) and certain cancers annually. Many FV and their juices contain flavonoids, some of which increase endothelial nitric oxide synthase (eNOS) activity. A single nucleotide polymorphism in the eNOS gene, where thymine (T) replaces guanine (G) at position 894 predicting substitution of glutamate for aspartate at codon 298 (Glu298Asp), has been associated with increased CVD risk due to effects on nitric oxide synthesis and subsequently vascular reactivity. Individuals can be homozygous for guanine (GG), thymine (TT) or heterozygous (GT).


RESULTS
We investigated the effects of acute ingestion of a FV-puree-based-drink (FVPD) on vasodilation and antioxidant status in subjects retrospectively genotyped for this polymorphism. Healthy volunteers (n = 24; 11 GG, 11 GT, 2 TT) aged 30-70 were recruited to a randomized, controlled, crossover, acute study. We showed that acute consumption of 400 mL FVPD differentially affected individuals depending on their genotype. There was a significant genotype interaction for endothelium-dependent vasodilation measured by laser Doppler imaging with iontophoresis (P < 0.05) and ex vivo low-density lipoproteins (LDL) oxidation (P = 0.002). GG subjects had increased endothelium-dependent vasodilation 180 min (P = 0.028) and reduced ex vivo LDL oxidation (P = 0.013) after 60 min after FVPD compared with control, no differences were observed in GT subjects.


CONCLUSIONS
eNOS Glu298Asp genotype differentially affects vasodilation and ex vivo LDL oxidation after consumption of FV in the form of a puree-based drink.
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, The University of Reading, Whiteknights, Berkshire, UK.
Trevor W
TW
George
Saran
S
Waroonphan
Chutamat
C
Niwat
Michael H
MH
Gordon
Julie A
JA
Lovegrove
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001628:Beverages / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005638:Fruit / Q000737:chemistry*; D056726:Genetic Association Studies; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014463:Ultrasonography; D014664:Vasodilation; D014675:Vegetables / Q000737:chemistry*
D008077:Lipoproteins, LDL; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III