Mutation of hemostasis genes: manifestations and consequences

Mutation of the MTHFR gene is a problem associated with poor methylation and enzyme production. Mutations in the hemostasis genes MTHFR affect each person differently. Sometimes they lead to subtle symptoms, and sometimes they lead to serious, long-term health problems.

Although the exact prevalence rate is still a matter of debate, it is estimated that 30%-50% of all people may have a mutation in the MTHFR gene, which is inherited and passed from parent to child. As a rule, this is a heterozygous mutation. Approximately 14% to 20% percent of the population may have a more severe MTHFR mutation, which more dramatically affects overall health. It is called a homozygous mutation.

The difference is that a heterozygote is a mutation in one allele of a pair of genes. That is, the chance of its manifestation is 50%. A homozygote is a mutation in both alleles of a pair of genes, manifested in 100% of cases.

The MTHFR gene mutation was discovered during the completion of the Human Genome Project. The researchers realized that people with this type of inherited mutation were more likely to develop certain diseases. These include: ADHD, Alzheimer's disease, atherosclerosis, autoimmune disorders and autism.

There is still much to be learned about what this type of mutation means for people who carry it and go on to pass it on to their children.

Today, there are dozens of different health conditions associated with MTHFR mutations. But let us emphasize once again that even if you are a carrier of a mutation, it is not a fact that you will have its manifestations. Mutation only means increased risks.

Why is this dangerous?

Various mutations of hemostasis genes can lead to all sorts of pathologies in fetal development that are associated with blood clotting disorders. They are considered the cause of chronic inability to bear a fetus, which manifests itself in late miscarriages or other negative consequences. For this reason, it is important to undergo a timely examination.

Interpretation of results

In addition to genetic abnormalities, the study makes it possible to determine the cellular structure of hemostasis, which is extremely important for pregnancy management.

There are two types of gene disorders:

• the most dangerous polymorphism is homozygous, when the risk of thrombosis is extremely high;
• Heterozygous is considered less dangerous.

This is the basis for the principles of deciphering data obtained during a study on the probability of polymorphism:

1. No mutations were found, that is, the genes responsible for the elements of the hemostatic system did not undergo changes.
2. A mutation in heterozygous form means that a person is a carrier of a trait that can cause pathology.
3. Mutation in homozygous form. This means that two genes with anomalies were discovered, that is, the likelihood of characteristic pathologies is high.

Specialists will fully assess the degree of risk from pathologies associated with impaired blood clotting. They will also suggest the optimal prevention plan.

When do patients need testing for hemostasis gene mutations?

The process of mutation (polymorphism) is a fairly common phenomenon, and therefore tests are required in a number of cases.

• When a woman is selected the optimal option for hormonal contraception, or she undergoes a course of hormone replacement therapy.

In this situation, conducting a test will make it possible to choose the safest method so as not to harm the woman’s ability to conceive in the future. When else should you donate blood for hemostasis gene mutations?

• In the event that the patient consulted her doctor about her infertility or chronic inability to bear a fetus.

The presence of mutations in hemostasis genes, as a rule, is evidenced by repeated unsuccessful attempts at in vitro fertilization, along with late toxicosis, delayed fetal development and other symptoms. Even one of the listed signs will be enough to conduct an appropriate examination.

• The examination is also prescribed in cases where a woman has had cases of thrombosis before the age of fifty.

This is especially true for smoking patients, among whose close relatives there may have been cases of deep vein thrombosis, as well as strokes and myocardial infarction.

Mutation analysis

This is a diagnostic method that allows you to accurately identify predispositions to blood diseases, which is especially important before and during pregnancy. The analysis identifies genetic abnormalities that carry the risk of late spontaneous abortion, intrauterine developmental defects, fetal blood loss, and maternal blood cancer pathologies.

It was said above that congenital abnormalities of hemostasis genes may not manifest themselves in any way, but in critical circumstances for the body, for example, during pregnancy, childbirth or during surgery, dysfunctions associated with the process of blood clotting are sometimes detected, which can lead to dangerous consequences .

There is a list of hemostasis genes that are more often susceptible to mutation:

1. G20210A - prothrombin gene. Its changes are manifested by hereditary thrombophilias. The likelihood of thrombosis significantly increases the risk of developing heart attacks and strokes, and the use of contraceptive pills greatly increases the risk of blood clots. During pregnancy, a mutating gene causes miscarriage, premature placental abruption, and developmental delays in the unborn child.
2. G1691A is a factor 5 gene subject to Leiden mutation. The consequence is the likelihood of fetal death in the second and third trimesters.
3. FGB G455A - fibrinogen genes. Their changes lead to the formation of blood clots in the deep veins, thromboembolism, as well as problems with pregnancy.
4. MTRR and MTHFR are folate metabolism genes. Due to their anomalies, the fetus develops defects of the nervous system, heart and blood vessels, and urogenital organs.
5. MTHFR C677T is another gene that is responsible for folic acid metabolism. Due to its changes, the risk of developing atherosclerosis doubles, and the threat of the development of nervous system abnormalities in the fetus increases.
6. GPIa C807T is a glycoprotein gene. The consequences of mutations are thrombosis and thromboembolism, the risk of heart attacks and strokes in youth
7. PAI-1 4G/5G is the gene responsible for plasminogen activator inhibitor. Due to its mutational changes, pregnant women experience early and late miscarriages, gestosis, and premature expulsion of the placenta.

Considering that all gene abnormalities in one way or another affect the outcome of pregnancy, based on the results of the study, the couple will be able to decide not to plan it. This happens when there is too high a chance that pregnancy will have serious complications. This is not easy for many, but in such cases it is better to push emotions into the background, take a sober look at the situation and make a thoughtful decision.

What do doctors recommend?

Doctors advise taking all the necessary tests for mutations in hemostasis genes immediately before a planned surgical operation, such as transplantation or endoscopic prosthetics, and so on. Pathology of blood clotting as a result of serious intervention can cause serious complications, including the death of the patient. In addition, an examination should be carried out if a young person has hearing impairment, the cause of which cannot be determined. All of the above situations are the main cases when testing for diseases may be necessary.

Various mutations of hemostasis genes can also remain invisible to patients for many years, as they can occur without any symptoms and arise suddenly. True, at a stressful moment for the body, for example, during pregnancy or during surgery, blood clotting disorders may be detected, which can lead to the death of the fetus, as well as other dangerous consequences.

The main reasons for the formation of mutations

Mutations in the genes of the hemostasis system are congenital and are passed down through generations. In view of this danger, a check is required, especially if the appearance of thrombosis and blood incoagulability was noticed among close relatives. True, there are also acquired mutations that arise under the influence of various factors.

One of the main reasons is the so-called antiphospholipid syndrome, which is an autoimmune disease against which the human body produces antibodies against its own phospholipids. Autoimmune pathologies, as a rule, occur infrequently, however, hemostasis mutations can also form for other reasons.

These are regular stressful situations that reduce the body's resistance to various infections. In addition, during constant overexertion, various functions in the body may be disrupted.

Presence of cancer or endocrine diseases. Some of these are related to the environmental situation. It has already been proven that in some areas, cancerous tumors, along with all kinds of gene mutations, are much more common due to environmental pollution due to human activities.

Taking pharmaceutical drugs, especially hormonal ones. An examination is required before using hormonal contraceptives in order to avoid their negative and rather dangerous effects on the human body.

In which genes do mutations occur?

Genes provide a repair (restoration) mechanism: when a section of DNA is damaged, enzymes in the cells of our body “cut out” it and restore the original version.
The breakdown of this mechanism is the essence of gene mutation. We can inherit mutations in hemostasis, the blood coagulation system, on the paternal or maternal side. There are also so-called mutagenic factors that cause gene polymorphism in a completely healthy person - these are dangerous chemicals, ionizing radiation, work in high temperatures and retroviruses.

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Genes, “defects” of which create a tendency to bleeding or, conversely, to increased blood clotting and thrombosis, are:

• FGB – responsible for fibrinogen, the 1st plasma coagulation factor;
• G20210A – prothrombin gene, the second coagulation factor;
• F5, Leiden – proaccelerin, the fifth, so-called Leiden factor;
• F13A1 – fibrinase gene, thirteenth plasma factor;
• ITGB3 – platelet receptor gene for the first factor, integrin and others.

In the laboratory of hemostasis pathology at the MLC on Zemlyanoy Val, studies are carried out on more than 20 types of hemostasis polymorphisms. Hemostasiologists have a special rating scale that determines the risk of thrombosis and spontaneous bleeding. It also takes into account the results of blood tests:

1. On the activity of protein C and free protein S, which are involved in the inactivation of the 5th and 8th blood coagulation factors. Hereditary deficiency of proteins C and S leads to obstetric complications: preeclampsia, fetoplacental insufficiency and neonatal disseminated intravascular coagulation syndrome.
2. Activity and inhibitor ADAMTS13 is a plasma enzyme that cleaves von Willebrand factor. Inherited deficiency of ADAMTS13 can cause microvascular occlusion, hemolytic anemia, and HELLP syndrome.
3. The sail test, which is used to detect genetic thrombophilia - the risk of developing thrombosis, blockage of a vessel with a blood clot.

Additional risk group

There are quite a lot of factors influencing the occurrence of mutations in hemostasis genes. An additional risk group, among other things, may include people suffering from severe obesity, against which certain types of injuries can lead to the appearance of gene mutations. At the moment, it is not known exactly on the basis of what principle gene mutations arise, although world medicine has now learned to minimize the consequences of this polymorphism. At the first suspicion, tests are required, and this should be done at the stage of the woman’s pregnancy planning.

Hemostasis genes most frequently affected by mutation

When visiting the clinic, patients are asked to undergo an extensive examination. Thus, direct analysis for mutations of hemostasis genes is carried out in relation to:

• Prothrombin gene. Mutations of this type are expressed in the form of congenital thrombophilias, due to which vascular thrombosis is likely, and, in addition, the risk of heart attacks and strokes increases significantly. The use of contraceptive medicinal products can several times increase the risk of blood clots. Among pregnant women, a mutation of this gene results in the inability to bear a fetus, as well as placental abruption and delayed embryonic development.
• The next type is the Leiden mutation, which is manifested by changes in the fifth factor gene. The symptoms in this case are similar to the previous option. Also, this type of mutation is characterized by fetal death, usually during the second, maximum third trimester.
• Mutations of fibrinogen genes manifest themselves in the form of deep vein thrombosis, as well as thromboembolism. In this case, miscarriage and, as a consequence, miscarriages in early and later stages are likely.
• Mutations in folic acid metabolism genes can lead to defects in the development of the nervous system in the pregnant fetus. Pathologies of blood vessels, heart and urogenital apparatus are not excluded. A blood test for mutations in hemostatic genes must be taken by all women who are planning a pregnancy, especially those who are at risk.

• If mutations occur in the folic acid metabolism gene, this leads to disruption of the enzyme methylenetetrahydrofolate reductase, which converts the substance homocysteine ​​into methionine. In situations where doctors observe a similar process in patients, the risk of atherosclerosis almost doubles, and in addition, the possibility of giving birth to a child with serious abnormalities of the nervous system increases. In addition, such children may experience anencephaly along with severe mental retardation and other types of damage.
• In the case of the glycoprotein gene, mutations are accompanied by thrombosis and thromboembolism, which significantly increases the risk of strokes and myocardial infarction at a young age. Mutational changes can be inherited, for this reason this factor should be taken into account when planning pregnancy, especially if there have already been miscarriages.
• Mutations in the gene that is responsible for plasminogen activator inhibitor can cause miscarriages both early and later. In addition, this causes gestosis, placental abruption and other negative consequences. Timely identification of such a mutation makes it possible to reduce the risk of their manifestation during pregnancy and childbirth.

There are also some genes whose status will be analyzed during the study. Depending on the results obtained, the couple will be able to decide whether it is worth planning a child at all, because in the presence of probable pathologies, the risk of complications is high. Such a decision is never easy, but it is necessary to soberly assess the level of risk, and in addition, make a thoughtful and informed decision.

Now analysis for mutations of hemostasis genes can be carried out in Invitro. It's fast and inexpensive.

How to reduce the risk of negative symptoms of MTHFR mutation

Consume more natural folate, vitamin B6 and vitamin B12

In the case of folate cycle gene mutations, it is important to eat plenty of foods rich in vitamins B6, B9 and B12.

You can also take them as a supplement. However, remember that people with MTHFR mutations have a more difficult time converting the synthetic form of folic acid into a bioavailable form. Moreover, taking regular folic acid may worsen symptoms.

Getting enough folic acid is especially important before and during pregnancy. In the three months before conception and during the first trimester of pregnancy, mothers who get enough folic acid reduce their children's risk of developing a variety of health problems.

It is critical for people with MTHFR mutations to get bioavailable forms of folate in a supplement called L-methylfolate or the methyl form of vitamin B9.

L-methylfolate is more difficult to package in capsule form, so you may not be able to get very high doses in a typical multivitamin or supplement. Therefore, it is recommended to take a mono supplement called 5-MTHF.

Related articles:

• Vitamin B12 overdose - symptoms
• Vitamin B9 - use, symptoms of deficiency and excess

Now Foods, Methyl Folate, 5,000 mcg, 50 Vegetarian Capsules

Thorne Research, 5-MTHF, 5 mg, 60 capsules

If you have been diagnosed with a homozygous MTHFR mutation, then you need to take folic acid methyl complexes continuously in courses - at least 3 times a year.

Having more folic acid in your diet means you are better able to create the active form of 5-MTHF. Some of the best foods high in folic acid include:

• Beans and lentils
• Leafy green vegetables such as raw spinach
• Asparagus
• Romaine
• Broccoli
• Avocado
• Colorful fruits such as oranges and mangoes

Another way to obtain materials

Today there is another way to obtain materials for analysis purposes. Thus, some clinics use a cheek swab, which allows you to obtain epithelial cells located on the back of the cheeks. This method is an absolutely painless and fairly quick option. This measure is an opportunity to conduct an examination without unnecessary discomfort, especially for those who are afraid of injections. Upon completion of laboratory tests, doctors schedule a consultation with a hematologist, who will have to explain and comment on the results in detail. This analysis is carried out using the polymerase chain reaction method; determination of the result becomes possible thanks to control samples.

How is hemostasis gene research performed?

Testing for hemostasis

The performance of the hemostasis system can be analyzed in several ways: capillary and venous blood can be used as test material; samples must be taken on an empty stomach. It is advisable to find out the laboratory’s work schedule in advance and refrain from eating spicy or salty foods the day before so that the test results are not distorted.

Now there is another way to obtain material for analysis: some clinics use a cheek swab, which allows you to obtain epithelial cells from the back of the cheek. This method is completely painless and very fast; it is an opportunity to conduct an examination without discomfort, even for people who are afraid of injections. After laboratory tests, a consultation with a hematologist is scheduled, who will explain the results in detail.

When conducting laboratory tests, the fact that during pregnancy the level of blood clotting always increases slightly, and this is not a pathology, is taken into account. However, the presence of mutations enhances this process, and the onset of thrombosis can cause great harm to the body of the mother and child.

To check whether the mutation is inherited, it is recommended to undergo a genetic test. This is an expensive procedure, which makes it possible to determine the likelihood of further deviations in the hemostatic system in descendants. This type of test is necessarily prescribed to people who have already had cases of thrombosis in their family.

Any doctor can refer you for testing, and the reasons for diagnosis will be such conditions as:

• phlebeurysm;
• vein thrombosis;
• pregnancy planning;
• fetal death at the intrauterine stage of development;
• prescription of hormone replacement drugs and oral contraceptives;
• placental abruption;
• intrauterine anomalies of fetal development;
• fetoplacental insufficiency and toxicosis;
• early miscarriages;
• stroke;
• myocardial infarction;
• thromboembolism at a young age, as well as its recurring episodes;
• excess body weight;
• upcoming surgery;
• cardiovascular pathologies in blood relatives;

In addition, analysis for gene mutations of the hemostatic system is recommended in cases such as:

• infertility;
• upcoming in vitro fertilization (IVF) procedure;
• the presence of signs of bleeding (including from the gums, from small cuts received during shaving), small bruises on the body;
• menstruation accompanied by abnormally high blood loss;
• the need to assess the condition of the liver.

For the analysis, you need to donate blood from a finger and a vein on an empty stomach. In some clinics, a cheek swab is taken, through which a sample of the epithelium of the inside of the cheek is obtained. It is painless and quick, which makes it possible to examine those who are pathologically afraid of injections, for example, children. After the results are ready, a consultation with a hematologist is indicated, who will professionally describe them.

The study is carried out using the PCR method, which stands for polymerase chain reaction. The obtained data are compared with control samples. It is taken into account that when carrying a child, the level of blood clotting always increases slightly. This is not considered a pathology, but if there are mutations, the process is aggravated.

To find out how high the risk is that the mutation will be inherited, doctors advise taking a genetic test. This is expensive, but this type of study is highly recommended for those who have already had cases of thrombosis in their family. It is important to understand that mutations in hemostasis genes that are not detected in a timely manner can cause fetal death or lead to severe developmental defects.

Definition of genetics

In order to determine whether this is inherited, it is recommended to take tests to determine genetics. Such an expensive procedure will help determine the likelihood of possible deviations in the hemostatic system in future offspring. This type of test is prescribed to patients who have a history of thrombosis in their family. It is definitely worth sounding the alarm, since a mutation that is not identified in time can lead to the death of the fetus or to severe defects in its mental and physical development.

Deciphering the mutation of hemostasis genes should be carried out by a highly qualified specialist.

Is it possible to correct violations?

Medicine answers this question positively, since thanks to modern methods it is possible to combat increased blood clotting and also prevent placental insufficiency. For this purpose, folic acid is prescribed, which prevents the formation of blood clots, and doctors also prescribe special multivitamins and other necessary medications. If medical recommendations are strictly followed, the chance of carrying a healthy child along with a successful birth without complications increases to ninety-five percent.