title: The MTHFR 677 C/T polymorphism influences plasma levels of adhesion molecules and nitric oxide.
abstract: BACKGROUND
  Hyperhomocysteinemia is an independent risk factor for cardiovascular events. The T allele of 677 C/T polymorphism at the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to induce mild hyperhomocysteinemia. In the present study, we investigated the relationship between this polymorphism and adhesion molecules and total nitric oxide (NOx).
  
  
  METHODS
  The adhesion molecules tested in the present study were soluble E-selectin (sE-selectin), vascular adhesion molecule (sVCAM), and intercellular adhesion molecule (sICAM). A total of 297 subjects had data on these atherosclerotic biomarkers and the MTHFR genotypes. The genetic effect was estimated in the multivariate regression models with adjustment of covariates. Homocysteine, folate, vitamin B6 and vitamin B12 levels were measured in 181 subjects for the test of association between the biomarkers and homocysteine levels.
  
  
  RESULTS
  The genotype distribution was in Hardy-Weinberg equilibrium. The sVCAM levels increased with the number of the T allele, while the NOx levels decreased with the number of the T allele. We found that the T allele was significantly associated with high sVCAM levels (p=0.002) and low NOx levels (p=0.011) in the regression models. The MTHFR genotypes were associated with homocysteine levels (p=0.031). Mild hyperhomocysteinemia (>12 micromol/L) was significantly associated with sVCAM levels (p=0.036). The NOx levels were lower in the hyperhomocysteinemia group than in the normal homocysteine group, but the difference was not significant. The genotypes were not significantly associated with either sE-selectin or sICAM.
  
  
  CONCLUSIONS
  The detrimental T allele exerted an additive effect to increase sVCAM and decrease NOx concentrations, which may contribute to atherosclerosis.
authors: Graduate Institute of Medical Genetics, Kaohsiung Medical University, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Suh-Hang Hank
authors: SH
authors: Juo
authors: Yi-Chu
authors: YC
authors: Liao
authors: Chen-Ling
authors: CL
authors: Kuo
authors: Yihsin
authors: Y
authors: Wang
authors: Ching-Shan
authors: CS
authors: Huang
authors: Hui-Chin
authors: HC
authors: Chiang
authors: Chin-San
authors: CS
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000097:blood*; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011110:Polymorphism, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D009569:Nitric Oxide; D025101:Vitamin B 6; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12