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MTHFR Mutation

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Also known as: MTHFR DNA Testing
Formal name: Methylenetetrahydrofolate Reductase Mutations, C677T and A1298C

The Test Sample

What is being tested?

The methylenetetrahydrofolate reductase (MTHFR) gene contains the DNA code to produce the MTHFR enzyme. This test detects two of the most common mutations.

When there are mutations or variations in the MTHFR gene, it can lead to serious genetic disorders such as homocystinuria, anencephaly, spina bifida, and others. The MTHFR enzyme is critical for metabolizing one form of B vitamin, folate, into another. It is also part of the process that converts homocysteine into methionine, an important building block for many proteins.

If someone has increased levels of homocysteine, that means the body is not processing it properly. One cause of that could be a mutation in the MTHFR gene, causing homocystinuria. While at least seven unique MTHFR mutations have been found in people with homocystnuria, there are two relatively common DNA sequence variants, known as single nucleotide polymorphisms (SNPs) that are tested. The two MTHFR variants are called C677T and A1298C, and individuals can inherit one or both variants. These SNPs result in changes in the DNA (or mutations) that are associated with increased homocysteine levels in the blood, which may increase the risk of premature cardiovascular disease (CVD), formation of inappropriate blood clots (thrombosis), and stroke.

Approximately 5-14% of the U.S. population is homozygous for C677T, meaning that they have two copies of it. There is some ethnic variability in the frequency, with the highest being in those of Mediterranean ancestry and the lowest in those of African ancestry.

The C677T variant results in a less active form of the MTHFR enzyme and reduced ability to process folate and homocysteine. When a person has two copies of the MTHFR C677T gene mutation (homozygous) or one copy of MTHFR C677T and one copy of A1298C (compound heterozygous), decreased MTHFR enzyme activity slows down the homocysteine-to-methionine conversion process and can lead to a buildup of homocysteine in the blood.

The increase in homocysteine is often mild to moderate but will vary from person to person depending upon the amount of MTHFR enzyme activity. Even if a person has two copies of the MTHFR mutation, that person may not develop high homocysteine levels since adequate folate intake can "cancel out" the effect of the MTHFR mutation.

Results of some studies suggest that high levels of homocysteine in the blood may contribute to risk of CVD by damaging blood vessel walls and promoting formation of plaque (atherosclerosis) and inappropriate blood clots. However, a direct link between homocysteine levels and cardiovascular disease or thrombotic risk has not been found. For more on this, see the article on Homocysteine.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.