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

Mol Nutr Food Res. 2012 Jul;56(7):1014-24. doi: 10.1002/mnfr.201100689. Epub 2012 Jun 12.

Abstract

Scope: 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).

Methods and 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.

Conclusion: eNOS Glu298Asp genotype differentially affects vasodilation and ex vivo LDL oxidation after consumption of FV in the form of a puree-based drink.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Beverages / analysis*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control
  • Cross-Over Studies
  • Endothelium, Vascular / diagnostic imaging
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Fruit / chemistry*
  • Genetic Association Studies
  • Humans
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / chemistry
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidation-Reduction
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Ultrasonography
  • Vasodilation*
  • Vegetables / chemistry*

Substances

  • Lipoproteins, LDL
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III