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MTHFR DNA Test

The MTHFR DNA Test (MTHFR = Methylenetetrahydrofolate Reductase)

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This information describes a test for a change in the MTHFR gene. It contains an introduction to understanding how genes and DNA work in our body and what role the MTHFR gene has.  The MTHFR gene/DNA test is most often done to look for changes called polymorphisms which are different to mutations.

In summary

    1. MTHFR polymorphisms are different to MTHFR mutations
    2. MTHFR polymorphisms are very common in the general population whereas mutations are rare
    3. According to current research, MTHFR polymorphism testing does not provide information that is useful for clinical decision making.

Our DNA

In all the cells of our body our genetic material, or DNA, is packaged on string like structures called chromosomes. Our DNA contains important information (genes) that is used by the cells in our body to make proteins that help us grow and function properly.  We have two copies of every gene, one that we inherit from our mother and one from our father.

What are DNA polymorphisms?

Although we all usually have the same number and types of genes, there are small variations called polymorphisms (poly means many; morphisms means forms) that make us unique.  Polymorphism is the word used for common DNA changes that are considered harmless to our health. These harmless changes can occur throughout our DNA.

Some polymorphisms may change the gene message in a way that reduces how well the resulting protein works.  However, they usually do not have a strong impact on our health.

What are DNA mutations?

Mutations are less common DNA changes which cause a gene to become faulty and not produce the correct protein. The protein may be less efficient or not working at all when there is a mutation in a gene. This can lead to health consequences in some situations. 

What is MTHFR?

MTHFR is the name of a gene found in our DNA which contains the instructions on how to make a protein called ‘methylenetetrahydrofolate reductase’. Methylenetetrahydrofolate reductase helps our bodies metabolise or process folic acid, which is important for general health and has been shown to be particularly important during the early stages of pregnancy for the developing baby.

MTHFR polymorphisms.

MTHFR polymorphism testing is sometimes undertaken as a part of investigating a number of health problems including blood clotting conditions and recurrent pregnancy loss. More recently, research has shown testing for the MTHFR polymorphisms does not provide reliable or useful health information in many circumstances. Therefore this test may not provide an answer to the reason why an individual is having these problems. If testing has been done, however, it is important to understand what the results mean.

A number of polymorphisms have been identified in the MTHFR gene. The two most commonly reported polymorphisms are called C677T and A1298C. These polymorphisms are common among the general population and do not cause a severe change in the ability of the MTHFR gene to function in the usual way. Having one or both of these polymorphisms may reduce the efficiency of the protein produced by the gene, but the effect is small enough that even people who have inherited a polymorphism from both parents (ie affecting both copies of their gene) are unlikely to develop significant medical issues as a result (see table 1 for more details).

There is more information about what it means to have an MTHFR polymorphism in table 1 below

MTHFR mutations

These occur far less frequently than polymorphisms. A mutation in the MTHFR gene can lead to a severe deficiency, or absence of the MTHFR protein in the body. A genetic condition known as homocystinuria is caused by having a mutation on BOTH MTHFR genes (inherited from the mother and the father). Having homocystinuria can lead to vascular problems (problems with blood vessels or blood circulation) and other symptoms.

If you are found to have one or more MTHFR mutations, it is important that you discuss this with your doctor who may refer you to a specialist genetic clinic.

Remember: MTHFR mutations are different to MTHFR polymorphisms

What does it mean if an MTHFR polymorphism is found following a DNA test?

Since we all have two copies of each of our genes (one from our mother and one from our father), DNA testing may reveal either one or two copies of a polymorphism in a person’s MTHFR gene. MTHFR polymorphisms are common and many people with various combinations of them have been extensively researched.

Looking at the most common polymorphism and their possible combinations, the table below explains what the anticipated outcome would be and what would happen next if testing showed someone was carrying a polymorphism(s) in their MTHFR gene.

 

TABLE 1 – Potential MTHFR polymorphism test results
Remember some results will be completely normal – i.e. no polymorphism or mutation found

MTHFR Genetic test result

Expected outcome and possible further treatment

C677T hetrozyogote (CT)

This means that one copy of your MTHFR gene has a polymorphism called C677T and the other copy has no polymorphism

Approximately 30% of the population will get this result. This does not usually cause any health concerns.

Some practitioners might recommend vitamin supplementation, but there is little evidence to support that this is necessary.

A1298C hetrozyogote (AC)

This means that one copy of your MTHFR gene has a polymorphism called A1298C and the other copy has no polymorphism

This result does not usually cause any health concerns.

Some practitioners might recommend vitamin supplementation, but there is little evidence to support that this is necessary.

C667T/A1298C compound hetrozyogote (CT/AC)

This means that one copy of your MTHFR gene has a polymorphism called C677T and the other copy has one called A1298C

This result does not usually cause any health concerns

Some practitioners might recommend vitamin supplementation, but there is little evidence to support that this is necessary.

A1298C homozygote (CC)

This means that both of your MTHFR genes have the same polymorphism known as A1298C

This result does not usually cause any health concerns

Some practitioners might recommend vitamin supplementation, but there is little evidence to support that this is necessary.

C677T homozygote (TT)

This means that both of your MTHFR genes have the same polymorphism known as C677T

Some people with this result may develop a mild to moderate increased blood homocysteine level or hyperhomocysteinaemia. This alone does not usually cause any symptoms or health problems, however further testing may be recommended.

Having high levels of homocysteine is a risk factor for a number of cardiovascular (heart and circulation) problems.

Hyperhomocysteinaemia is multifactorial, meaning that it needs a combination of factors: (genetic, physiological and environmental) to become a problem and cause symptoms. Reduced MTHFR enzyme activity is only one risk factor and people with both C677T MTHFR polymorphisms may have mild to moderate hyperhomocysteinaemia.  A vitamin B supplement may reduce homocysteine levels, however more research is still needed to determine whether this will actually reduce the risk of having cardiovascular symptoms in the future.

MTHFR, Folate and Neural tube defects.

Neural tube defects such as spina bifida and anencephaly are partly caused by a lack of the B group vitamin called folate or folic acid in the mother i.e. in the pregnancy environment in which the baby is developing before birth.

Research has shown that 7 out of 10 (70%) cases of neural tube defects can be prevented by increasing the mother’s intake of folate prior to, and during, early pregnancy.

It is recommended that for all women, regardless of their MTHFR genetic testing result, folate supplements (0.5mg per day) be taken for a least 1 month prior to possible conception and continued at that level for the first 3 three months of pregnancy.

Reference

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Scott E. Hickey, Cynthia J. Curry, Helga V. Toriello Genetics in Medicine(2013)15,153–156doi:10.1038/gim.2012.165

 

 

Last updated: Sep 17, 2014