Leah Burke, MD, is a pediatric geneticist at the UVM Medical Center and a professor at the Larner College of Medicine at the University of Vermont.

Have you heard of MTHFR testing? You probably will. Here’s the information you need to make an informed decision about it.

What is MTHFR?

According to the Internet, MTHFR is a gene responsible for everything from fatigue and impotence to vaccination reaction and autism. But, that’s not right.

As a pediatric geneticist, I am here to tell you that MTHFR is the acronym for a gene responsible for the 5,10-methylenetetrahydrofolate reductase enzyme. Say what? This enzyme plays a role in the metabolism of folate, one of the B vitamins naturally present in some foods and added to others. Reduced activity of this enzyme is a risk factor for elevated levels of an amino acid called homocysteine. High levels of homocysteine are a risk factor for blood clots and other heart-related diseases. But, many factors may lead to high levels of homocysteine, as you will learn in this article.

How common are variations in the MTHFR gene?

Very common, it turns out. We estimate that 25 percent of people of Hispanic descent and 10-15 percent of people of North American Caucasians descent carry two copies of one of the most common of the variants. Studies on the association of MTHFR variants and medical complications show no consensus for any cause-and-effect relationship.

Should my family members and I get screened for MTHFR?

No. The American College of Medical Genetics and Genomics, the American College of Obstetrics and Gynecology, The American Heart Association, and the College of American Pathologists have all come out with statements against screening for MTHFR mutations.

Medical research has not proven that the presence of the common MTHFR variants are a risk factor for blood clots, pregnancy loss, or other negative pregnancy outcomes, nor for cardiovascular disease.

But, what about if I or my partner are planning a pregnancy?

If a mother has a history of clotting problems or recurrent pregnancy loss, we do not recommend MTHFR testing. However, we recommend a thorough evaluation of other causes, as there may be treatments for those. A pregnant woman should continue to take folate, regardless of whether she has a MTHFR variant or not. Having the common MTHFR variants does not change the dose of folic acid recommended.

But, I heard about MTHFR variant testing in an advertisement.

Direct-to-consumer advertising for MTHFR variant testing is widespread. There is no evidence-based medicine to support the use of testing. The bottom line is that folate is important for good health. That is why foods are fortified with it, and why we encourage eating leafy green vegetables. Knowing your MTHFR status does not change that.

What if I already found out my MTHFR variant status? What does it mean for me?

The overall risk associated with the common MTHFR variants is small, so small that their presence does not change treatment. This is why we do not recommend testing for the variants. Very high homocysteine levels rarely result from having the common variants alone.

We recommend that people with very high homocysteine levels undergo evaluation for other factors known to affect homocysteine. These can include hypothyroidism, chronic conditions (obesity, diabetes, high cholesterol, physical inactivity, high blood pressure), medications (atorvastatin, fenofibrate, methotrexate, and nicotinic acid), dietary deficiencies (folate, vitamin B6, vitamin B12), smoking, and advanced age.

If none of these are present in a person with very high homocysteine levels, a consultation with a genetics professional may be helpful in identifying rare genetic causes of the high homocysteine.

Learn more about Pediatric Genetics at the UVM Medical Center. 

Leah Burke, MD, is a pediatric geneticist at the UVM Medical Center and a professor at the Larner College of Medicine at the University of Vermont. 

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