MTHFR stands for methylenetetrahydrofolate reductase. It attracts attention because of a genetic mutation that can lead to high levels of homocysteine and low levels of folate and other vitamins in the blood. It may seem like a bad word at first glance, but it has to do with a relatively common genetic mutation. There was concern that some health problems were associated with MTHFR mutations, so testing has become more common over the years.
MTHFR
Variants of the MTHFR Mutation
Methylenetetrahydrofolatereductase (MTHFR) is the rate-limiting enzyme in the methyl cycle and is encoded by the MTHFR gene. It catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is a co-substrate for the re-methylation of homocysteine to methionine.
People may have one or two mutations in the MTHFR gene (or both). These mutations are often called variants. A variant is a part of the DNA of a gene that generally differs (or can vary) from person to person. Having one variant (heterozygous) does not cause health problems. Some people believe that two mutations (homozygous) can cause more serious problems. There are two variant (form) mutations that can occur in the MTHFR gene.
- Some 30 to 40 percent of the American population may have a mutation in the gene position C677T. Some 25 percent of people of Hispanic descent and 10 to 15 percent of Caucasian descent are homozygous (with two mutations) for this variant.
- About 20 percent of the American population may have a homozygous mutation at gene position A1298C.
- It is also possible to obtain compound mutations C677T and A1298C (one copy of each).
Gene mutations are inherited, which means you get them from your parents. Conceptually, if you get a mutant copy of the MTHFR gene from each parent, you will have a homozygous mutation and increase your risk.
What Are the Symptoms of an MTHFR Mutation?
Symptoms vary from person to person and from variant to variant. Keep in mind that research on MTHFR and its effects is still developing. Evidence linking many health conditions to MTHFR is currently incomplete or unproven. You probably will not know if you have the MTHFR mutation unless you have this genetic test.
Complications associated with having homocysteinemia due to MTHFR mutations include:
Some non-MTHR-related causes of high homocysteine include:
- Hypothyroidism
- Conditions such as diabetes, high cholesterol, and high blood pressure
- Obesity and inactivity
- Certain medications such as atorvastatin, fenofibrate, methotrexate, and nicotinic acid
Diagnosis
As mutations on the MTHFR gene are point mutations, the best and the most accurate method to diagnose the problem is via Real-Time qualitative Polymerase Chain Reaction (RT qPCR). PCR assays are good not only for the detection of possible mutation but also to identify the exact position and type, as well as the homozygous or heterozygous status of the mutation. The fluorescent dye in the specific probe emits light only when bound to its target. In the RT qPCR method, the targets are the known mutation sequences of the MTHFR gene, such as A1298C or C677T, therefore light emission precisely specifies the presence or absence of the condition. By using different florescent dyes, the PCR method enables scanning for multiple mutation sites in one reaction tube, allowing a very small sample volume.
Recurrent miscarriages and neural tube defects are potentially associated with MTHFR. One study suggests that women with two C677T variants may be twice as likely to have a child with a neural tube defect. Another study looked at women with a history of recurrent miscarriages. It found that 59% of patients had multiple homozygous gene mutations, including MTHFR, associated with blood clotting, with only 10 percent of women in the control category.
What Could Be Potential Treatment?
The MTHFR gene mutation interferes with the way the body processes folic acid and other important B vitamins. In these cases, doctors may recommend supplements to address deficiencies, along with medications or treatments to address certain health conditions. Modifying the supplementation of this nutrient is a potential focus to counteract its effects.