title: Endothelial nitric oxide synthase and methylenetetrahydrofolate reductase gene polymorphisms are associated with endothelial dysfunction in young, healthy men.
abstract: BACKGROUND
  The guanine to thymine polymorphism at position 894 of the eNOS gene (resulting in a change from glutamate to aspartate [Asp] at codon 298 [Asp298]) and the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) have been reported to be associated with atherosclerosis and cardiovascular disease. Endothelial dysfunction is considered to be the earliest stage of atherosclerosis.
  
  
  OBJECTIVE
  To examine whether common eNOS and MTHFR gene polymorphisms are associated with endothelial dysfunction in young, healthy men without overt cardiovascular disease.
  
  
  METHODS
  Flow-mediated, endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced, endothelium-independent vasodilation (GTN) were measured using high-resolution ultrasound of the brachial artery in 53 young, healthy men assigned to eNOS and MTHFR genotypes.
  
  
  RESULTS
  Subjects with the eNOS Asp298 allele (n=15) showed significantly reduced FMD:GTN compared with those without this allele (n=38) (0.23+/-0.13 [mean +/- SD] versus 0.35+/-0.14, P=0.0072), whereas there was no significant difference in GTN between these two groups. Although subjects with the MTHFR T677 allele did not show significantly reduced levels of FMD:GTN, subjects with the eNOS Asp298 allele and who were carriers of the MTHFR T677 allele demonstrated markedly reduced levels of FMD:GTN compared with noncarriers (0.14+/-0.05 versus 0.28+/-0.13, P=0.04).
  
  
  CONCLUSIONS
  The data suggest that even in young men, the eNOS Asp298 allele may be involved in endothelial dysfunction before any overt vascular disease has occurred. Furthermore, a combination of the eNOS Asp298 and MTHFR T677 alleles may exaggerate endothelial dysfunction and may contribute to a comparatively earlier development of atherosclerosis.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Imamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Mizuno
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Imai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Sakai
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000175:diagnosis / Q000235:genetics; D001483:Base Sequence; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics; D004730:Endothelium, Vascular / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2)