DISEASE INFORMATION
Genetic risk factors are involved in the predisposition of individuals to venous thrombosis. The most
common mutation associated with inherited thrombosis is Factor V Leiden G1691A mutation and results in
resistance to activated protein C. The second most common mutation associated with hereditary thrombosis
is the G20210A mutation in the prothrombin (Factor II) gene. Increased plasma homocysteine level is
another risk factor for venous thrombosis, and is associated with homozygosity for a genetic variant in
the methylene tetra-hydrofolate reductase (MTHFR) gene. The MTHFR gene produces an enzyme that helps
regulate homocysteine levels in the body by catalyzing the conversion of 5,10-methylene-tetrahydrofolate
(5,10-methylene-THF) to 5-methyltetrahydrofolate (5-methyl-THF), which can methylate homocysteine to form
methionine. The mutated C677T MTHFR gene results in a thermolabile MTHFR, with reduced activity, resulting
in a higher level of homocysteine in the blood. The higher homocysteine levels may cause irritation of the
blood vessels. Elevated levels of homocysteine show an increased risk for atherosclerosis, which could
eventually result in a heart attack and/or stroke, and blood clots in the veins, referred to as venous
thrombosis. Individuals with two copies of 677C (677CC) have the most common genotype. 677TT individuals
(homozygous) have lower MTHFR activity than CC or CT (heterozygous) individuals. To have any detrimental
effect, mutations must be present in both copies of a person’s MTHFR genes. The variant is commonly found
in North American, European, and Asian populations, with the highest frequencies among Southern
Mediterranean and Hispanic populations in North America.