About the Thrombotic Risk DNA Panel
The thrombotic risk DNA panel will determine whether you carry any of the mutations in the F2, F5 and MTHFR genes that are known to increase the risk of thrombophilia.
This test is available to anyone but is particularly valuable for individuals who have a family history of blood clots or have family members who have suffered from the following conditions:
• A blood clot at a younger age (under 50 years)
• An “unprovoked” clot with no apparent cause
• A clot caused by pregnancy, birth control pills or hormone replacement therapy
• A clot occurring in an unusual place (e.g. liver, kidney, gut, brain)
• A history of more than one vein clot.
Genes Tested in the Thrombotic Risk DNA Panel
The thrombotic risk DNA panel identifies the presence or absence of the following mutations which are associated with an increased risk for thrombophilia:
• Leiden mutation: 1691G>A in the F5 gene encoding Factor V
• Prothrombin mutation: 20210G>A in the F2 gene encoding Prothrombin
• MTHFR mutations: 677C>T and 1298A>C in the MTHFR gene encoding methylenetetrahydrofolate reductase.
Factor V Leiden Mutation (F5)
The F5 gene encodes a protein (Factor V) that promotes blood clotting. In the normal situation, the Factor V protein is inactivated by another protein called Protein C. This inactivation occurs by cleaving of the Factor V protein at three different arginine amino acids (at positions 306, 506 and 679). However, when the Factor V Leiden mutation occurs, the resulting protein resists inactivation and increases the risk of abnormal clotting. The Leiden mutation is a single base substitution (1691G>A) that changes an arginine at one of the cleavage points to a glutamine (Arg506Gln). The Leiden mutation can also be referred to as c.1601G>A or p.Arg534Gln.
The Factor V Leiden mutation is associated with an increased relative risk of thrombophilia and is also associated with a 2- to 11-fold increased relative risk for miscarriages. Individuals who are heterozygous for the Factor V Leiden mutation have between a 3- and 8-fold increased risk of thrombophilia. The risk is higher in individuals that have two copies of the Factor V Leiden mutation (homozygotes). Several different studies have predicted a wide range of relative risk values with an increased risk for homozygotes estimated to be anywhere between 10- and 80-fold.
Factor II Prothrombin Mutation (F2)
The F2 prothrombin gene encodes the prothrombin protein that promotes blood clotting. When the 20210G>A mutation (a.k.a. c.*97G>A) occurs in the prothrombin gene, more of the prothrombin protein is produced, hence an increased chance of blood clotting.
Individuals who are heterozygous for the 20210G>A prothrombin mutation have a 2- to 5-fold increased risk of thrombophilia. The risk is higher in individuals that have two copies of the 20210G>A mutation (homozygous).
The MTHFR gene encodes the methylenetetrahydrofolate reductase (MTHFR) enzyme that helps process Vitamin B9. Vitamin B9 is also known as folic acid or folate and is required in the process of converting homocysteine to methionine. When either the 677C>T or 1298A>C mutation occurs in the MTHFR gene, the enzyme is not as efficient at processing Vitamin B9/folate and an excess of homocysteine accumulates, leading to abnormal blood clotting.
The 677C>T mutation (a.k.a c.665C>T) is a single base substitution (C>T) that changes an alanine to a valine (p.Ala222Val) and reduces the MTHFR enzyme level to ~25% of normal. The 1298A>C mutation (a.k.a. c.1286A>C) is a single base substitution (A>C) that changes a glutamic acid to an alanine (p.Glu429Ala) and reduces the MTHFR enzyme level to ~60% of normal.
An increased risk of high homocysteine levels (and associated thrombophilia) only occurs when an individual has either two copies of the 677C>T mutation or one 677C>T and one 1298A>C allele. If an individual only has one 677C>T or one 1298A>C allele there is no increased risk of high homocysteine as the wildtype allele provides enough functional MTHFR to produce folate to prevent the build up of homocysteine. Interestingly, the presence of two 1298A>C alleles is also not associated with an increased risk.
High homocysteine levels due to MTHFR variants and/or other risk factors have also been linked to pregnancy complications including miscarriages, placental abruption (where the placenta pulls away from the wall of the uterus) and preeclampsia (high blood pressure and proteinuria).
Thrombotic Risk DNA Panel Specifications
None. This test can be taken at any age.
Buccal swabs. The test kit contains buccal swabs and instructions for collecting a buccal swab sample from inside the mouth.
Four buccal swabs, rubbed inside the mouth against the cheek for 15 seconds.
1 – 2 weeks.
Laboratory specimens are analyzed using sequence-based typing to detect the presence of the four mutations that increase the risk of thrombophilia (1691G>A in F5, 20210G>A in F2 prothrombin, 677C>T and 1298A>C in MTHFR). Analytical specificity and sensitivity for detection of these alleles are >99%. Other alleles not listed are not detected.
DNA test kits do not have an expiry date and can be used at any time. Once the DNA sample is collected, it must be returned to the laboratory for testing within three months of collection. No refrigeration is required. Store at room temperature.
It is important to remember that the presence of one or more of these four mutations does not mean that an individual will definitely develop thrombosis. Although each of these mutations increase the risk of thrombophilia to varying degrees there are many individuals that have these alleles and never experience thrombosis. There are also people that do not have these alleles who are at risk of thrombophilia due to other mutations or health or environmental factors.
Next, Understanding Your Thrombotic Risk DNA Test Results »
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