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

TY - JOUR

T1 - 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

AU - George, Trevor W

AU - Waroonphan, Saran

AU - Niwat, Chutamat

AU - Gordon, Michael H

AU - Lovegrove, Julie A

N1 - © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Amino Acid Substitution

KW - Beverages

KW - Cardiovascular Diseases

KW - Cross-Over Studies

KW - Endothelium, Vascular

KW - Female

KW - Fruit

KW - Genetic Association Studies

KW - Humans

KW - Lipoproteins, LDL

KW - Male

KW - Middle Aged

KW - Nitric Oxide Synthase Type III

KW - Oxidation-Reduction

KW - Polymorphism, Single Nucleotide

KW - Retrospective Studies

KW - Vasodilation

KW - Vegetables

U2 - 10.1002/mnfr.201100689

DO - 10.1002/mnfr.201100689

M3 - Article

C2 - 22689471

SN - 1613-4125

VL - 56

SP - 1014

EP - 1024

JO - Molecular Nutrition & Food Research

JF - Molecular Nutrition & Food Research

IS - 7

ER -