The MTHFR 677 C/T polymorphism influences plasma levels of adhesion molecules and nitric oxide.
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.
Juo
Suh-Hang Hank
SH
Graduate Institute of Medical Genetics, Kaohsiung Medical University, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Liao
Yi-Chu
YC
Kuo
Chen-Ling
CL
Wang
Yihsin
Y
Huang
Ching-Shan
CS
Chiang
Hui-Chin
HC
Liu
Chin-San
CS
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
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