Genetic risk of trombophilia, folate metabolism (MTR, MTRR, MTHFR)

The analysis is based on the simultaneous determination of gene mutations affecting folate metabolism.

Folate metabolism is integrated into the most important cellular processes (amino acid metabolism, nucleotide synthesis, DNA methylation, etc.). Disorders of folate metabolism negatively affect DNA stability, can contribute to the development of cancer, and also lead to the accumulation of homocysteine in cells and an increase in its level in blood plasma. High concentration of homocysteine leads to damage to the walls of the vascular bed, activation of the blood clotting system, increases the aggregation activity of platelets, contributes to an increase in cholesterol and the development of atherosclerosis, may be the cause of chronic pregnancy failure, congenital abnormalities of the fetus, various kinds of depression, senile dementia, Alzheimer's disease.

Causes of folate cycle disorders:

• genetic defects of folate cycle enzymes (MTHFR, MTR, MTRR);
• folic acid deficiency;
• deficiency of vitamins B6 and B12.

Additional risk factors for folate cycle disorders:

• pathology of the stomach and intestine with impaired absorption of vitamin B12;
• malignant neoplasms of the pancreas and intestine;
• kidney pathology;
• long-term and chronic infections;
• diet;
• long-term use of methotrexate, anticonvulsants, other drugs antagonists of folic acid, drugs that disrupt the absorption of folates;
• hemodialysis;
• smoking.

In order to timely identify the risk of developing an undeveloped pregnancy, it is recommended to monitor biochemical parameters and determine the presence of polymorphisms of folate metabolism in the first weeks of pregnancy. The test of mutations in the folate cycle genes – MTHFR, MTRR and MTR – allows us to determine underlying risk for fetoplacental insufficiency, non-infection of the neural tube, non-divergence of chromosomes in meiosis and other fetus pathologies incompatible with life.

If available:

• hyperhomocisteinemia;
• cardiovascular diseases (coronary heart disease, ischemic stroke, arterial hypertension, atherosclerosis, thrombosis);
• preeclampsia;
• habitual miscarriage of pregnancy;
• congenital malformations of the fetus (isolated defects of the neural tube in the fetus, cleft upper lip and palate), chromosomal abnormalities of the fetus;
• oncological diseases (colorectal cancer, breast cancer, ovaries cancer);
• migraines, depression, insomnia, chronic fatigue syndrome, headaches, memory loss.

For these genes, there is no concept of "norms" and "pathologies," because gene polymorphisms are being investigated. The interpretation of the results of the analysis should be carried out by the attending physician, taking into account the medical history, the results of other genetic analysis, clinical manifestations, and laboratory data.

The MTHFR gene (1298 A/C):

• The A/A genotype is not associated with a change in enzyme activity.
• A/C is a genotype predisposing to a decrease in enzyme activity in combination with 677T and 1298C.
• C/C is a genotype predisposing to a decrease in enzyme activity.

The MTHFR gene (C677T):

• The C/C genotype is not associated with a change in enzyme activity.
• C/T is a genotype predisposing to a decrease in enzyme activity in combination with 677T and 1298C.
• T/T is a genotype predisposing to a decrease in enzyme activity.

The MTR gene (2756 A/G):

• The A/A genotype is not associated with a change in enzyme activity.
• A/G is a genotype predisposing to a decrease in enzyme activity in combination with 2756G and 66G (MTRR).
• G/G is a genotype predisposing to a decrease in enzyme activity.

The MTRR gene (66 A/G):

• The A/A genotype is not associated with a change in enzyme activity.
• A/G is a genotype predisposing to a decrease in enzyme activity in combination with the heterozygous allele 66G and 2756G (MTR).
• G/G is a genotype predisposing to a decrease in enzyme activity.