18 January 2017

Cardiology needs genetics

Anna Govorova, Infox.ru

The entire XX and XXI century is, of course, first of all, discoveries in genetics, which largely set the trend for the development of all medicine, reports Infox

It is worth remembering the discovery of the Sanger sequencing method in 1974, the Human Genome project, which lasted more than 10 years, the discovery of the new generation sequencing method (NGS) at the beginning of this century.

Now in most developed countries of the world, genetic research has become a routine diagnostic method in cardiology and is fully funded by the state. In our country, genetic diagnostics is still an expensive and inaccessible method, which not all specialists are ready to work with.

But it is already clear that this direction will develop, and many clinical cases prove how necessary it is.

Cholesterol and hereditary cholesterol are different things

Probably everyone knows that an excessive amount of "bad" cholesterol in the blood leads to the development of atherosclerosis, threatens with heart attacks and strokes.

But modern cardiology says that in order to correctly diagnose, determine what is the risk of a patient developing cardiovascular diseases with high cholesterol (more than 7.5-8 mmol / l), genetic studies are needed.

Here it is important to find out whether the patient has familial hypercholesterolemia (CGS). That is, a hereditary disease with a high risk of developing cardiovascular complications and a high probability of damage to relatives. If everything is normal with an elevated cholesterol level with heredity, the treatment tactics are the same. But if you are not very lucky with genetics, then the disease can proceed in a completely different way, more serious treatment is often required.

"The disease (CFS) may be asymptomatic, especially in children. And if it is not diagnosed in time and not treated, then the risk of developing coronary heart disease increases by 20 times. And men who have not received treatment have a 50% increased risk of fatal and non-fatal myocardial infarctions under the age of 50. In women, this risk is 30% higher at the age of 60," says Natalia Sonicheva, cardiologist, member of the scientific committee of the genetic laboratory Health in Code (Spain).

Another alarming sign is that CFS can cause 5% of cardiac arrests in people younger than 60 years and 20% younger than 45 years.

It is very important that a genetic analysis for CGS can also be carried out in children, starting from the age of five, if mom or dad has familial hypercholesterolemia. Then, according to modern recommendations, the doctor, if necessary, can prescribe statins from 8-10 years of age.

"There are a lot of hereditary cardiovascular diseases"

Genetic research in cardiology is very important in other hereditary cardiovascular diseases. "These diseases have one important property in common – a heterogeneous clinic, so it is difficult to diagnose them. As a rule, they are family, and the mechanism of inheritance is autosomal dominant - when there are sick relatives in each generation, half of the relatives will be sick," says Natalia Sonicheva.

There are a lot of such hereditary cardiovascular diseases. If we add together cardiomyopathies, electrical myocardial diseases, hereditary aortic diseases and familial hypercholesterolemia, which is more common than others, it turns out that in Russia it is about 850 thousand people.

Of course, it is very important to diagnose these diseases at an early stage, Natalia Sonicheva emphasizes, then it allows you to prescribe the right treatment.

Medical Detective

"For example, in our practice there was such a clinical case. Here is such a family: a 79–year–old woman with arterial hypertension, her sister has atrial fibrillation, stroke, hypertrophic cardiomyopathy. My sister also has a seventeen–year-old granddaughter with a completely different clinical picture, severe symmetrical concentric hypertrophy of the left ventricle, and my mother has no abnormalities on EchoCG. That is, it is surprising that three generations have a different clinic," says Natalia Sonicheva.

Here it was important to understand how to treat the girl. A genetic study revealed that the whole family, all three generations, are carriers of a mutation in troponin I, the gene encoding the sarcomere protein. This mutation leads to the development of classical hereditary hypertrophic cardiomyopathy. It turns out that if there is one mutation, then the clinic in all three generations should be similar. But the clinic was completely different.

And then, with the help of another genetic study, cardiologists found out that the girl has another mutation in the gene encoding the protein tyrosine phosphokinase, responsible for the cascade complex of mitogen-activated protein kinases, which are responsible for cell proliferation, differentiation and apoptosis. With violations in this cascade, diseases of rasopathy develop, such as Noonan, Leopard syndromes, etc., requiring completely different treatment tactics and having a more unfavorable prognosis.

Genetics helps prevent death

Another reason why it is necessary to carry out genetic diagnostics is the early detection of affected relatives, because the main threat of all hereditary cardiovascular diseases is sudden cardiac death, which can occur with complete well–being at a young age.

"For example, such a clinical case: there are two brothers in the family, one dies of sudden death at the age of 20 on the background of physical exertion, the other brother at 22 - almost immediately after the death of the first (playing football). There is also a sister in this family, who, of course, is just scared. We conducted a genetic study and found a malignant mutation leading to the development of catecholaminergic ventricular tachycardia, where the main cause of death is sudden death at a young age on the background of exercise or stress. In our database, we already have information about the same mutation that occurred in eight families, among them there were 16 sudden deaths under the age of 40. And if the genetic diagnosis had been carried out at least after the death of the first brother, it would have been possible to save the second patient simply by prescribing beta-blockers. The girl, fortunately, is not a carrier of this mutation, she is completely healthy. Only on the basis of genetic diagnosis was it possible to draw such a conclusion," says Natalia Sonicheva.

The most important thing here is the interpretation of the data

Genetic studies are extremely important for risk stratification and disease prognosis. Knowing the mutation and its localization, it is possible to determine the prognosis of the disease for each specific variant and give recommendations for the management of the patient, but for this the key point is the interpretation of the genetic research data first by bioinformatics to determine the pathogenicity of the mutation (unfortunately, there are very few qualified bioinformatics in our country so far), molecular biologists to determine functional disorders in the protein, caused by the mutation, and at the last stage – cardiologists who will give practical recommendations for the management of patients and the prevention of complications.

Portal "Eternal youth" http://vechnayamolodost.ru  18.01.2017

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