Posted on 30 January 2020

What is the MTHFR gene and what does it do?

MTHFR stands for Methyl-Tetra- Hydro- Folate Reductase. It is an enzyme: a protein that catalyzes a chemical reaction in our body, converting folate to (as the name implies) methyl-tetra-hydro-folate.  It has become known colloquially (a little unfairly) as the mother-f#$%er gene.

The MTHFR gene is the area of DNA that provides our bodies with the instructions to code and produce the MTHFR enzyme. The enzyme is an important element of the folate metabolic pathway, helping our bodies to regulate blood levels of the amino acid homocysteine.

What is a gene mutation?

Humans all come from a small founder population of common ancestors. Genes in their original working forms are known as “wildtypes”.

A gene mutation is where, during the process of gene “photocopying” that goes on when our body’s cells replicate and divide, a mistake is made.

The code for a gene affects the shape and function of the gene’s protein product. Sometimes the new version is an improvement – better at it’s job than the original protein.

Sometimes a mutation means the protein product works less well than the original or not at all. A serious defect in a protein’s function caused by a genetic mutation can cause disease.

The  MTHFR gene was sequenced in the early 1990’s and since then it has been appreciated that there are 3 main forms of the gene is human populations.

The Wildtype: 677CC / 1298AA

Variations on the Wildtype, known as “Polymorphisms”: C677T,

A1298C . These are DNA changes that are very common in our population – both in fertile and non-fertile men and women.

All three forms of the gene create MTHFR enzymes that work ok, but the wildtype codes for a protein that works a bit better than either of the described polymorphisms, which work about 40% less well than the wildtype of the gene.

It is thought that MTHFR polymorphisms may have widely spread in southern Mediterranean populations and that the mutations spread because they may actually be helpful in context of surviving malaria.

What happens to a person if the MTHFR gene really doesn’t work?

Homocysteinuria is a disease that presents very early in a person’s life, affecting children whose MTHFR gene have serious mutations causing the MTHFR enzyme to malfunction. Patients with homocysteinuria have, amongst other serious problems including neuro-developmental problems, a higher risk of stroke and blood clots. This is a severe metabolic disease with recessive genetic inheritance, meaning you need 2 bad copies of the gene to suffer the disease. Having just one good, working copy of the MTHFR (either the wildtype or one of the polymorphisms) is enough to stop a person suffering from homocysteinuria. This phenomenon is called haplotype sufficiency which means – one working copy of the gene is enough.

When the MTHFR gene polymorphisms were discovered, scientists and doctors hypothesized that some issues suffered by people with homocystinuria might affect people with MTHFR polymorphisms in a much milder form. Since the 90’s, the gene types have been widely studied in women with fertility problems including IVF failure and miscarriages and we’ve learned a lot.

We now appreciate that MTHFR polymorphisms do not cause disease, but can be thought of as a risk factor for disease, especially in women who do not take or do not absorb supplemental folate.

Taking 400mcg of folate or folinic acid (methylated folate) per day is enough to stabilize the enzyme activity of MTHFR polymorphisms, helping them work better. Folate is a really important building block for making babies and all women trying to conceive, regardless of their MTHFR genotype, should use supplemental folate.

Having enough folate is especially important for women who have MTHFR polymorphisms and also for women who have had pregnancies affected by spinal cord defects or miscarriages in general.  Most women don’t need to use higher doses of folate, but daily doses up to 5mg should be used by women Examples include women with type 1 diabetes, women with epilepsy, or women who have had a previous pregnancy affected by a spinal cord problem.

What’s the take home message: REMEMBER TO TAKE YOUR FOLATE!

If you are taking folate but not absorbing it well, you may be advised to switch to folinic acid (methylated folate).

If your folate status is replete (you are absorbing well and have plenty) you need not worry about your MTHFR gene status

If your folate status is low, having a MTHFR polymorphism may be a risk factor for disease.

If you’d like to learn more about the MTHFR Gene contact reception at Women’s Health Melbourne to book in for a private consultation.



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