A common mutation in methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is associated with reduced enzyme activity, a thermolabile enzyme and mild hyperhomocysteinemia, a risk factor for vascular disease.
A milder deficiency of MTHFR, with 30%-50% residual enzyme activity and increased enzyme thermolability, has been described as a risk factor for vascular disease and for neural tube defects.
CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C(677)T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease.
We also examined whether vitamin cofactors and the C677T genetic mutation of the methylenetetrahydrofolate reductase (MTHFR) enzyme were major contributors to elevated plasma tHcy and carotid vascular disease.
Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme activity and were associated with the susceptibility to different disorders, including vascular disease, neural tube defects and lymphoid malignancies.
It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs.
Mutations in the methylenetetrahydrofolate reductase (MTHFR) enzyme, which is involved in homocysteine metabolism, have been investigated as potential vascular disease risk factors.
The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy.
DNA from 247 older subjects with vascular disease and 594 healthy subjects without vascular disease (in three different control groups) was screened for the MTHFR 677 C-to-T mutation.
The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, may play a role in the development of not only vascular disease but also diabetic microangiopathies.
Some recent studies suggested that a mutation in the gene encoding for 5-10 methylenetetrahydrofolate reductase (MTHFR), due to a transition C-->T at nucleotide 677, is a genetic risk factor for vascular disease.
C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease.
The C677T substitution variant in the methylenetetrahydrofolate reductase (MTHFR) gene has been associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease.
Hyperhomocysteinemia, a risk factor for vascular disease, is related to vitamin B12, vitamin B6, and especially folate deficiency, or to genetic factors such as mutations in methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the remethylation pathway of homocysteine to methionine.
Individuals with the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), due to homozygous C677T MTHFR gene mutation, have significantly raised plasma levels of homocysteine and may be at increased risk of vascular disease.