The three genes associated with an increased risk of thrombophilia are all located on autosomal chromosomes – F5 and MTHFR on chromosome one and F2 on chromosome eleven. Autosomal chromosomes are inherited in pairs - one from each parent. Therefore each individual can inherit two normal copies of an autosomal gene (homozygous normal), or two copies that carry a genetic mutation (homozygous mutant), or one normal copy and one mutated copy (heterozygous). It is possible to inherit several different combinations of the F5, F2 and MTHFR genes, and each combination is associated with a different risk of thrombophilia.
The thrombotic risk DNA panel offered by SwabTest identifies the F5 Leiden mutation (1691G>A), the F2 prothrombin mutation (20210G>A) and two mutations in the MTHFR gene (677C>T and 1298A>C).
The F5 Leiden mutation is associated with the highest thrombotic risk, as heterozygotes have up to an 8-fold increased risk, while homozygotes can have up to an 80-fold increased risk.
Individuals that have one or two copies of the F2 prothrombin mutation also have an increased risk, but not as high as the risk associated with the F5 Leiden mutation.
Two defective MTHFR genes are required, with at least one carrying the 677C>T mutation, before there is an increased thrombotic risk. Other unknown factors are also required in conjunction with the defective MTHFR genes, before individuals are affected by increased homocysteine levels and the associated risk of thrombophilia.