MTHFR Mutations: What Are They? What role do they play in pregnancy?

What happens when there is an MTHFR mutation? What are the therapies to deal with pregnancy?

Mthfr is an acronym that indicates the enzyme methylene-tetrahydrofolate reductase , involved in the chain of reactions which, starting from dietary folate, lead to the methylation of homocysteine , converting it into methionine, using vitamin B12 as a cofactor.

There are different types of mutation in the gene that codes for this enzyme, based on the position on the gene on which the mutation occurs and whether the mutation occurs in homozygosity or heterozygosity.

Mutations in the MTHFR gene

As regards the position, the most frequent mutations are

  • C677T
  • A1298C

In the first case, in position 677 on the gene which codes for the mthfr enzyme, a C (cytosine, nitrogenous base) has been replaced with a T (thymine, another nitrogenous base);

In the second case in position 1298 the substitution of nitrogenous bases concerned an A (adenine) replaced with a C (cytosine).

Mutations in heterozygosity or homozygosity: what is the difference?

Genes are made up of alleles and each allele is present in two copies, one inherited from the mother and one from the father.

The mutation can be on only one of the two alleles, and in this case we speak of heterozygous or it can be on both, and we speak of homozygous.

The mutation is RECESSIVE, i.e. it is expressed when both mutated alleles are present, i.e. in the condition of homozygosity. Anyone who has a heterozygous mutation is considered a healthy carrier , the functionality of the enzyme is maintained, even if in a “reduced version” (as seen in the first of the two figures).

What happens when there is an MTHFR mutation?

As we said initially, the mthfr enzyme is involved in a series of biochemical reactions which convert dietary folate into 5-methyl-tetrahydrofolate (5-MTHF), which in turn transfers the methyl group to homocysteine, producing methionine , an amino acid.

If this biochemical pathway doesn’t work properly, there is a slowdown of this conversion, with homocysteine ​​accumulation and increased cardiovascular risk, thrombophilia, as well as the probability of spontaneous abortion in women.

For this reason, women who have frequent miscarriages or have MTHFR mutations are ordered to have their blood homocysteine ​​checked.

What therapy in case of MTHFR Mutations?

Treatment generally consists of increasing dietary folate intake and supplementation with methylfolate.

Sometimes folic acid supplementation is used, but this leads to several problems:

  •  folic acid is synthetic and not fully bioavailable. What we take with food are folates , present in various chemical forms and with variable bioavailability, but, all in all, sufficient in normal pathophysiological conditions.
  • with the intake of folic acid, a first chemical reaction is required to convert it into dihydrofolic acid, catalysed by the enzyme dihydrofolate reductase. This reaction is very slow compared to the rest of the chain of reactions, so folic acid tends to accumulate, risking interacting with other biochemical processes.
  • if mthfr is mutated and conversion to 5-MTHF greatly reduced , effective supplementation involves the already methylated form of folate, i.e. methylfolate.

To find out if an mthfr mutation is present, a genetic analysis must be done , through a blood sample or with a saliva sample.

In the event of a mutation, the ideal is to consult a nutritionist for suitable nutrition and, if necessary, the right integration.

Kathryn Barlow is an OB/GYN doctor, which is the medical specialty that deals with the care of women's reproductive health, including pregnancy and childbirth.

Obstetricians provide care to women during pregnancy, labor, and delivery, while gynecologists focus on the health of the female reproductive system, including the ovaries, uterus, vagina, and breasts. OB/GYN doctors are trained to provide medical and surgical care for a wide range of conditions related to women's reproductive health.

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