The MTHFR Gene—What is it?

MTHFR stands for methylenetetrahydrofolate reductase, a gene located on chromosome 1p36.3. This gene encodes a specific enzyme in the body, necessary to convert the molecule, 5,10-methylenetetrahydrofolate to 5 methyltetrahydrofolate.[3]

Why is MTHFR important?

The MTHFR gene is critical in amino acid processing. The successful conversion of homocysteine, a common amino acid in the blood, to methionine, strongly affects proper enzyme function.[1]

Too much homocysteine can be dangerous.

Elevated levels of plasma homocysteine may be linked to a number of medical conditions including:

• Cardiovascular Disease
• Cerebral Vascular Disease (Stroke)
• Venous and Arterial Thrombosis
• Methotrexate Toxicity for Cancer Therapy
• Increased dementia and Alzheimer’s disease
• Possible increase in bone fractures
• Higher rate of chronic heart failure
• Increased risk for preeclampsia (high blood pressure during pregnancy)
• Possible neural tube defects
• Cardiovascular death

*Individuals deficient in folate are especially vulnerable to high homocysteine levels.[5]

What is MTHFR Genotyping?

Defects in the MTHFR gene may cause homocysteine (potential toxic amino acid) levels to increase if the conversion to methionine (a necessary amino acid) is not successful. A test on whole blood can help identify possible defects.

Why MTHFR Genotyping Is Important

Elevated levels of homocysteine (hyperhomocysteinemia) may be due to the enzyme’s reduced activity, especially when folate is low in the body.

High homocysteine levels (>13umol/L) can put individuals at risk for developing certain medical conditions or other complications.

MTHFR genotyping can help isolate possible causes of high homocysteine levels and provide important information for treatment approaches.

MTHFR genotyping that reveals high homocysteine levels can help guide physicians and other healthcare practitioner in the development of a dietary plan that may include folate or folate with B6 and B12 vitamins.

Results of MTHFR testing may warrant an adjustment to the medication, methotrexate, prescribed to treat certain cancers, rheumatoid arthritis, and psoriasis.

Research studies have also linked MTHFR variants to possible ASD’s (autistic spectrum disorders), especially within the C677T polymorphism in the gene.[6]

Who Will Benefit From MTHFR Testing?

• Individuals who have high levels of homocysteine in the blood.
• Those with a family history of stroke, cardiovascular disease, or thrombosis.
• Patients who receive long-term methotrexate therapy.

What are genetic variants for MTHFR?

A genetic variant refers to an alteration in the common DNA sequence. It is often used in place of the older term “genetic mutation”.[2]

Each of us carries two copies of the MTHFR gene containing instructions for creating the enzyme that breaks down the amino acid, homocysteine.

Too much homocysteine can lead to serious medical conditions.

MTHFR Genetic Variants By Race

In the United States, two gene variants are most common, C677T and A1298C. Roughly 25% of Hispanics, and 15% of Caucasians have two copies of C677T.

Genetic Variants

C677T—A mutation (variant) from cytosine to adenine exists at position 677 within the gene.

A1298C—A mutation (variant) from adenine to cytosine exists at position 677 within the gene.

Each of these variants affects amino acids in the protein, reducing its function.

Possible Genotypes 677-CC, CT-TT

CC-homozygous normal
Roughly 45% of the population
No greater risk involved

CT-one variant copy
Roughly 45% of the population
Some reduction in enzyme activity
By itself, no greater risk involved

TT-two variant copies
Roughly 10% of the population
Increased risk for hyperhomocysteinemia and other complications

1298-AA, AC, CC

AA-normal homozygous

AC or CC- one or two copies of variants
Roughly 30% of the population
No increased risk on its own
Increased risk if combined with 677 variant[4]

MTHFR testing should be considered for all individuals at risk for homocysteine related conditions.