MTHFR Gene Polymorphism

MTHFR Gene Polymorphism - Understanding Its Role in Health and Disease

The MTHFR (methylenetetrahydrofolate reductase) gene plays a critical role in folate metabolism, a process essential for DNA synthesis, repair, and methylation. Variations or polymorphisms in the MTHFR gene can lead to reduced enzyme activity, affecting the body‘s ability to process folate into its active form. Two common MTHFR polymorphisms, 677C>T and 1298A>C, are found in a significant portion of the population, with about 60-70% of individuals having at least one of these variants. The clinical implications of these variants have been a topic of interest, particularly in relation to cardiovascular health, blood clotting disorders, pregnancy complications, and responses to certain medications like methotrexate.

While most individuals with MTHFR polymorphisms do not experience any noticeable symptoms, understanding these genetic variants is important for those at risk of health complications. Genetic testing for MTHFR polymorphisms can provide insight into potential health risks and guide personalized medical approaches

The MTHFR gene encodes the enzyme methylenetetrahydrofolate reductase, which is responsible for converting folate (vitamin B9) into its active form, 5-methyltetrahydrofolate (5-MTHF). This active form of folate is necessary for converting homocysteine, an amino acid, into methionine, which is used for various biochemical reactions in the body.

When there are polymorphisms in the MTHFR gene, such as 677C>T and 1298A>C, the activity of the enzyme can be reduced. This reduced enzyme activity can lead to elevated levels of homocysteine in the blood, a condition known as hyperhomocysteinemia. Elevated homocysteine levels have been associated with an increased risk of cardiovascular diseases, blood clot formation, and complications during pregnancy, including neural tube defects.

677C>T Variant: This variant results in a substitution of cytosine (C) with thymine (T) at position 677 of the MTHFR gene. Individuals who are homozygous for the 677C>T variant may have up to a 70% reduction in MTHFR enzyme activity, leading to higher homocysteine levels.
1298A>C Variant: In this polymorphism, adenine (A) is replaced by cytosine (C) at position 1298. While this variant generally has a milder impact on MTHFR activity compared to 677C>T, individuals who are compound heterozygous (having one copy of each variant) may still experience some reduction in enzyme activity and elevated homocysteine levels.

Clinical Utility of MTHFR Testing

MTHFR testing can offer valuable insights in the following clinical scenarios:

Cardiovascular Risk Assessment: Elevated homocysteine levels have been associated with an increased risk of cardiovascular diseases such as heart attacks, strokes, and blood clots (thrombosis). MTHFR polymorphisms, particularly 677C>T, can contribute to higher homocysteine levels, making genetic testing a useful tool for assessing cardiovascular risk in at-risk individuals.
Fertility and Pregnancy Complications: Certain MTHFR variants are associated with an increased risk of miscarriage, preeclampsia, and neural tube defects in newborns. MTHFR testing is often recommended for women with a history of recurrent pregnancy loss or those at risk of complications during pregnancy. For couples struggling with fertility, knowing their MTHFR status can guide appropriate interventions, such as folate supplementation.
Medication Response: MTHFR polymorphisms can affect how the body metabolizes certain medications, particularly methotrexate, which is commonly used in the treatment of cancers, autoimmune diseases, and ectopic pregnancies. MTHFR testing can help identify individuals who may need adjustments in their medication dosages to avoid adverse effects.
Neuropsychiatric Conditions: There is ongoing research into the potential association between MTHFR polymorphisms and neurological conditions such as depression, anxiety, and schizophrenia. Elevated homocysteine levels due to reduced MTHFR activity may impair neurotransmitter production, affecting mood and cognitive function.

When to Consider MTHFR Testing?

Family History: If you have a known family history of MTHFR gene mutations or family members who have experienced health complications related to these variants, testing may be recommended. Early detection can guide preventive healthcare measures.
Fertility and Pregnancy Issues: Couples experiencing difficulties with fertility, recurrent pregnancy loss, or complications during pregnancy, such as preeclampsia or neural tube defects, should consider MTHFR testing. Women who have a personal or family history of these conditions can benefit from testing to assess their risk and take preventive measures, such as increased folate supplementation.
Blood Clotting Disorders: Individuals who have a personal or family history of blood clotting disorders (thrombophilia) or cardiovascular diseases may benefit from MTHFR testing. Knowing the presence of MTHFR variants can help guide lifestyle changes and medication strategies to reduce the risk of clot formation.
Response to Medications: Testing may be useful for individuals who are undergoing or planning to undergo methotrexate therapy, particularly for cancer treatment or autoimmune diseases. Knowing MTHFR status can help healthcare providers adjust treatment plans to minimize side effects.

MapmyGenome Offerings

MapmyGenome provides comprehensive MTHFR genetic testing that analyzes both the 677C>T and 1298A>C variants. Our testing services offer detailed reports that include:

Carrier Status: Identify whether you carry one or more copies of the MTHFR gene variant.
Risk Assessment: Understand your risk for conditions associated with MTHFR polymorphisms, including cardiovascular diseases, fertility complications, and response to specific medications.
Personalized Recommendations: Based on your genetic profile, receive tailored recommendations for lifestyle changes, dietary adjustments, and possible supplementation with active folate (5-MTHF) to support healthy folate metabolism.
Genetic Counseling: Our genetic counselors are available to guide you through the process, from testing to interpretation of your results, ensuring you have the support you need to make informed healthcare decisions.

Test Specifications

Technique	Variant types	TAT	Sample requirements
Sanger sequencing	Mutation	3 - 4 weeks	2 ml EDTA Blood / 2 ug DNA