MTHFR Mutation

What is the MTHFR mutation? MTHFR is methylenetetrahydrofolate reductase  enzyme that is essential in the metabolism of homocysteine. Mutation in the gene for MTHFR is one of the most common inherited thrombophilias.

Homocysteine is a nonessential amino acid produced in the human body as a by-product of the metabolism of essential acids methionine. During normal functioning metabolism of the cell, homocysteine is quickly converted into further useable and harmless substances.

Folate is important for many metabolic processes, including the methylation of homocysteine and synthesis of nucleotides, neurotransmitters, proteins and phospholipids. Changes in the MTHFR gene may therefore result in increased levels of homocysteine in the blood, so called hyperhomocysteinemia. This may, however, also   be caused by a lack of vitamins (folic acid, B6 and B12) in food, which is a problem of current civilized society.

MTHFR MutationEffects of homocysteine

Homocysteine is characterized by high chemical activity, which may, when it is accumulated in the blood, overgrow into aggressiveness and toxicity. Through point mutations in MTHFR gene arises enzyme with increased thermolability and reduced activity. This is  significantly associated with higher level of homocysteine in plasma. Homocysteine (cytotoxic to endothelial cells), inhibits cell proliferation, and stimulates proliferation of smooth muscle cells in blood vessels. Additionally, homocysteine supports prothrombotic activity in the vessel wall which can result in atherosclerosis and thrombosis. Homocysteine inhibits the expression of thrombomodulin on endothelium, and thereby activation of protein C.  Hyperhomocysteinemia is also accompanied by increased activity of factor XII and factor V in the blood plasma.

Types of MTHFR mutation

There are two polymorphisms of MTHFR reducing its activity:

  1. A1298C polymorphism lies in f adenine for cytosine in1298 nucleotide.
  2. C677T The most frequent mutation of this gene is a point mutation (substitution) of C (cytosine) for T (thymine) at position 677, resulting in substitution of amino acid alanine (Ala = A) for valine (Val) at the point 223 in the peptide chain.

Relative risks of MTHFR mutation

Thermolabile C677T polymorphism is considered  a risk factor for neural tube defects.. Fetuses of homozygous mothers have a relative risk of neural tube defects increased about 2 times compared to fetuses of mothers with normal genotype. When a woman has a folate deficiency, this risk may increase up to 5 times. In women, who have been diagnosed with a handicapped   fetus, were observed to have   higher levels of homocysteine. We should add that the very diagnosis of mutations in the MTHFR gene still does not mean that an individual will actually have elevated homocysteine in the blood.

Diseases that can be correlated with higher homocysteine levels:

  • Cardiovascular diseases
  • Ulcers of the stomach and duodenum
  • Inflammatory bowel disease
  • Rheumatic joint disease, parkinsonism
  • Alzheimer’s disease, multiple sclerosis
  • Depression, migraine and chronic fatigue syndrome

Gynecologists, obstetricians and neonatologists take into account the previous group fertility disorders, premature births, miscarriages, developmental birth defects and also showed that these complications and failures can be avoided by sufficient doses of folic acid, vitamin B12 and vitamin B6 (pyridoxine). Folic acid and vitamin B6 deficiency in the diet is even potentiated with a higher content of fat in the diet, as these two vitamins are soluble in water and a greater amount of fat in the digestive tract impairs the conditions for its dissolution and, therefore, harder to absorb vitamins. This can explain the high rates of cardiovascular disease and increase in other diseases of civilization.

How to effectively prevent complications and adverse effects MTHFR?

As follows from the above results, for thrombophiliacs with MTHFR mutation and a higher risk of hyperhomocysteinemia, it   is extremely important to follow   a healthy lifestyle and balanced diet.

During pregnancy it is even more necessary to focus on adequate intake of folic acid, since in this way we can effectively reduce the risk of developmental defects in the fetus.

Folic acid in foods:

  • Leafy vegetables – all kinds of lettuce, cabbage

Vegetables – cauliflower, broccoli, kale, cabbage, tomatoes, beets, pumpkins, cucumbers, beans, peas

  • Grains – whole grain products, cereals, wheat germ
  • Fruit – mango, oranges, bananas, avocados, cherries, strawberries, raspberries, gooseberries
  • Nuts – walnuts, pistachios
  • Some dairy products – soft cheese, blue cheese
  • Meat – the highest content is in the intestines and liver, but a pregnant woman should eat liver in limited quantities

Thrombophiliac with MTHFR mutation must ensure adequate intake of folic acid and other B vitamins every day, but during pregnancy even much more.

Heredity of MTHFR mutation

It is an autosomal recessive type of inheritance. This type of inheritance is found in both sexes. Risk of occurrence of such individual is 25%. For this mutation to manifest, it is necessary, that the  bearer have both affected alleles in the genotype. Parents of affected person are therefore heterozygous for the trait, and the disease is not manifest in their case.

Heterozygous MTHFR has one healthy and one mutated allele – this means that the mutated allele can be imparted to children but it is not necessary. Descendants of this mutation in heterozygous form do not have to pass it on to the offspring. The chance of transferring mutated allele is 50%. When the couple of two heterozygous for this mutation meet, their baby may be completely healthy, may be heterozygous or may be homozygous for this mutation.

Occurrence of heterozygotes in European, North American and Australian population is 31% to 39% and the frequency of homozygotes 9% to 17%. Even here the codominant form of inheritance  takes place.

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