title: Endothelial nitric oxide synthase -786T>C, but not 894G>T and 4a4b, polymorphism influences plasma homocysteine concentrations in persons with normal vitamin status.
abstract: BACKGROUND
  Nitric oxide (NO) plays a relevant role in various events during atherogenesis. In vitro data suggest that NO may modulate homocysteine (Hcy) concentrations. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) -786T>C, 894G>T, and 4a4b polymorphisms in influencing Hcy concentrations.
  
  
  METHODS
  Blood samples were obtained from 1287 unrelated persons. Plasma Hcy was measured by fluorescence polarization immunoassay, folate and vitamin B(12) by RIA, vitamin B(6) by HPLC, and eNOS and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms by PCR with restriction fragment length polymorphism analysis.
  
  
  RESULTS
  MTHFR 677C>T polymorphism significantly influenced Hcy concentrations after adjustment for all confounding variables (P <0.0001 for trend). Univariate analysis showed that the eNOS -786T>C polymorphism, but not 894G>T and 4a4b, was significantly associated with the risk of having Hcy in the third tertile [>13.4 micromol/L; odds ratio (OR) = 1.2; 95% confidence interval (CI), 1.02-1.5; P = 0.03]. After adjustment for all variables known to influence Hcy, the -786T>C polymorphism still influenced Hcy concentrations (OR = 1.9; 95% CI, 1.1-3.2; P = 0.01). By analyzing the influence of eNOS polymorphisms on plasma Hcy concentrations according to vitamin concentrations (folate, vitamin B(6), and vitamin B(12)), age, and smoking habits, we found a significant association between the eNOS -786T>C polymorphism and Hcy in nonsmokers, in persons with normal vitamin status, and in persons <60 years.
  
  
  CONCLUSIONS
  The eNOS -786T>C polymorphism, but not 894G>T and 4a4b, influences plasma Hcy concentrations mildly but significantly and independently.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy. cinziafatini@hotmail.com
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.forename: Francesco
authors.initials: F
authors.lastname: Sofi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Meri
authors.initials: M
authors.lastname: Lenti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Casini
authors.forename: Calogero
authors.initials: C
authors.lastname: Surrenti
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005492:Folic Acid / Q000097:blood; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000097:blood / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood; D014815:Vitamins / Q000097:blood*
chemical_list: D014815:Vitamins; D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12