Mild hyperhomocysteinemia is an established risk factor for both arteriosclerosis and thrombosis, and may be caused by genetic and environmental factors.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyl-tetrahydrofolate, the cofactor for the methylation of homocysteine to methionine.
Individuals with the thermolabile variant of MTHFR have decreased MTHFR activities, resulting in elevated plasma homocysteine concentrations.
A homozygous 677C-T transition in the MTHFR gene has recently been identified as the cause of reduced enzyme activity and thermolability of the protein.
We studied the frequency of the homozygous mutant (+/) genotype in 471 patients with deep-vein thrombosis and 474 healthy controls enrolled in The Leiden Thrombophilia Study (LETS), its interaction with factor V Leiden, and assessed the association between the MTHFR genotypes and plasma homocysteine concentration.
Homozygosity for the 677C-T polymorphism was observed in 47 (10%) patients, and in 47 (9.9%) controls (OR 1.01 [95% CI : 0.7-1.5]). No modified risk of the (+/) genotype was observed in carriers of factor V Leiden.
Our data suggest that, although the homozygous mutant genotype is associated with elevated plasma homocysteine concentrations, this homozygous mutation itself is not a genetic risk factor for deep-vein thrombosis, irrespective of factor V Leiden genotype.
Mots-clés Pascal : Thrombose profonde, Veine, Facteur risque, Epidémiologie, Methylenetetrahydrofolate reductase (NADPH), Oxidoreductases, Enzyme, Mutation, Gène, Facteur V Leiden, Résistance, Protein C (activated), Serine endopeptidases, Peptidases, Hydrolases, Etude cas témoin, Pays Bas, Europe, Homme, Appareil circulatoire pathologie, Vaisseau sanguin pathologie, Veine pathologie, Hémopathie, Coagulopathie, Maladie héréditaire, Forme thermolabile
Mots-clés Pascal anglais : Deep vein thrombosis, Vein, Risk factor, Epidemiology, Methylenetetrahydrofolate reductase (NADPH), Oxidoreductases, Enzyme, Mutation, Gene, Factor V Leiden, Resistance, Protein C (activated), Serine endopeptidases, Peptidases, Hydrolases, Case control study, Netherlands, Europe, Human, Cardiovascular disease, Vascular disease, Venous disease, Hemopathy, Coagulopathy, Genetic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0119302
Code Inist : 002B12B03. Création : 22/06/1998.