Does the polymorphism 677C-T of the 5,10-methylenetetrahydrofolate reductase gene contribute to homocysteine-related vascular disease?

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disea se remains a matter of debate. Testing for the 677C-T nucleotide substituti on and assay of plasma homocysteine were carried out simultaneously in 69 c ontrols and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were ve ry similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interacti on between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting hom ocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of t he vascular disease but contributes to increased plasma homocysteine concen tration in conjunction with low plasma folate levels.