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It has become easier for Russian doctors to choose treatment for patients. Pharmacogenetics is developing in the country – a branch of medical genetics and pharmacology that studies the hereditary basis of drug effect variants and makes it possible to predict their safety. How it works in practice and why it has great prospects, Izvestia understood.

What is pharmacogenetics

The first hospital to implement such studies was the Central Clinical Hospital of the Administration of the President of the Russian Federation: it conducts tests that examine a group of key genes specific for the treatment of diseases. The results help the doctor decide what drug and dose is best to give the person so as not to “poison” him with inappropriate drugs. This became possible thanks to cooperation with the unique Institute of Personalized Medicine on the basis of the Russian Medical Academy of Continuous Postgraduate Education under the leadership of Academician of the Russian Academy of Sciences, D.A. Sychev.

Photo: Moscow City News Agency / Press Service of the Mayor and Government of Moscow / Maxim Mishin

As noted in the Central Clinical Hospital of the UDP RF, the introduction of pharmacogenetic markers of sensitivity to vital drugs helps to increase the effectiveness of treatment and increase the life expectancy of patients with cardiological, oncological, endocrinological, gastroenterological, neurological, infectious (including HIV, tuberculosis) and psychiatric profiles.

New methods help prevent a significant number of deaths due to the side effects of medications each year. Thanks to them, doctors can predict the development of health-threatening consequences of their use.

drug transformation

As Nikita Lomakin, head of the department of emergency cardiology, head of the department of cardiology of the RMANPO, chief cardiologist of the Administration of the President of the Russian Federation, explains to Izvestia, most of the drugs, before becoming an active drug, must undergo transformations in the human body. In the process of absorption, proteins are involved – carriers, which may be sensitive to certain substances. And either excessive or insufficient effectiveness of the drug will depend on the state of these proteins – both of which can be dangerous for the patient.

“And the very state of proteins depends on the genes that encode these proteins: in some people they are in an altered state,” says the doctor. “First, pharmacogenetics studies the proteins that are involved in drug metabolism, then the genes that encode these proteins, and then highlights the connections: do genetic changes affect the efficacy and safety of drugs.


Photo: Moscow City News Agency/Alexander Avilov

As an example, a cardiologist cites blood-thinning drugs: after heart surgery, millions of patients around the world are prescribed drugs that prevent blood clots. But many of them are prodrugs: if the drug does not pass the process of conversion in the liver due to proteins, it will not work in the body. Therefore, the efficiency and safety of the drug will depend on the speed with which the proteins perform their function by binding to the drug.

– There are three options: in the first, the drug will thin the blood well and give efficiency. In the second, it may turn out that the protein is changed so that the drug is not sufficiently converted into an active substance, it thins the blood poorly and blood clots can form. In the third, on the contrary, the protein digests the drugs too quickly – this will lead to an increased risk of bleeding, – says the interlocutor of Izvestia.

Different approaches

As the Professor of the Department of Clinical Pharmacology and Therapy named after Izvestia explains to Izvestia. Academician B.E. Votchala, Director of the Research Institute of Molecular and Personalized Medicine, Vice-Rector for Research and Innovation, FGBOU DPO RMANPO of the Ministry of Health of Russia Karin Mirzaev, in the case of pharmacogenetics we are usually talking only about “problem” medicines and difficult patients.

– There is no need to test for those who conditionally need here and now to prescribe a paracetamol tablet as an antipyretic. But this is relevant in cases with drugs that have a high risk of poor tolerance or insufficient effectiveness: for example, those with many adverse reactions indicated in the instructions, or drugs that are used by a large number of the populationMirzaev says.


Photo: TASS / Egor Aleev

According to Nikita Lomakin, Chief Cardiologist of the Administration of the President of the Russian Federation, few drugs have reached routine practice, for the appointment of which testing is recommended. But doctors have two approaches: population-based (everyone is treated “equally” in accordance with the standards and small groups of patients who need testing are identified) and personalized – “when a little more is done for the patient than prescribed in the recommendations.” And here, doctors can perform a large range of studies.

In the first case, scientists have developed rapid test systems – portable devices that determine the presence or absence of genetic changes within a few minutes. But they are provided only for a narrow range of indications. BUT everything that is not spelled out in these testimonies is considered personalized – for this there is a special genetic laboratory of RMANPO.

Testing in it is simple: patients are required to give a saliva sample, collected with a cotton swab from the inside of the cheek, or venous blood. The sample is sent for research, and after 4-7 days, the results of the analysis are reported to the person’s doctor.

– Then a detailed analysis comes, and the doctor sees which drugs the patient may be insensitive to, and which ones, on the contrary, will work effectively. And based on this, he can personalize the therapy,” says the cardiologist.


Photo: TASS / Artem Korotaev

According to him, Today, a large international database has already been created, where all pharmacogenetic information is loaded. Doctors can add information about the research they have done there – for example, that a certain gene affects the work of a certain drug in a certain way, so that everyone else can use this data. So physicians from all over the world can exchange experiences.

Who is researching

In the Central Clinical Hospital of the UDP RF pharmacogenetic studies are primarily carried out for people receiving blood thinning drugs: these include patients after stenting of the heart vessels – they must take medications from six months to a year, otherwise they may experience thrombosis and, as a result, a heart attack. However, up to 20-25% of patients are not sensitive to such drugs – tests can identify this group of patients and prescribe them another therapy that will be effective.says Nikita Lomakin.

“We also carry out studies for patients who receive antihypertensive, antiarrhythmic, oncological therapy, gastroprotectors, antidepressant therapy, cholesterol-lowering drugs – in some people, the latter can cause damage to muscle tissue. They happen to a few – but this is a formidable situation and it is better to immediately test in order to choose the right medicine, ”says the interlocutor of Izvestia.


Photo: Moscow City News Agency/Kirill Zykov

Of course, doctors prescribe treatment based not only on test results, they collect an anamnesis, study the patient’s symptoms, data from laboratory and instrumental research methods, comparing all this with clinical recommendations and their own experience. And only then select therapy.

Pharmacogenetics plays an important role: it deals with questions related to how the body will respond to a drug and how several prescribed drugs will interact with each other. To do this, scientists have developed special calculators that calculate the risks of complications when taking several drugs at once, and can choose an alternative.

Taking into account the features

According to doctors, today Russia, like other countries, is striving for a transition to personalized medicine. And pharmacogenetics is one of its most promising areas, which is already being successfully implemented in clinical practice.

Programs for the evaluation of pharmacogenetic characteristics are also operating in other countries, for example, Scandinavia and China. BUT In the United States, the first drug has already been introduced, the instructions of which indicate that it is especially effective for patients of a specific race – Negroid.

– For Russia, pharmacogenetics is even more relevant – our country is multinational, it is home to more than 100 ethnic groups that have differences in sensitivity to different drugs and their tolerance– says Karin Mirzaev.


Photo: RIA Novosti / Kirill Kallinikov

There are already achievements in this area: a scientific group led by Dmitry Sychev published a series of works in rating journals on the study of the pharmacogenetic characteristics of the peoples of Russia, in which any practitioner, scientist or biologist can find out which clinically significant markers are common in a particular ethnic group of the Russian Federation.

– In addition, our group from the Research Institute of Molecular and Personalized Medicine FGBOU DPO RMANPO of the Ministry of Health of Russia under the leadership of Academician Sychev of the Russian Academy of Sciences collected a large bioresource collection of samples of patients with various pathologies: psychiatric, gastroenterological, cardiological and others with an assessment of their pharmacogenetic characteristics in associative studies within the framework of grants Russian Science Foundation, and in certain areas – as part of the task of the Russian Ministry of Health. These studies make it possible to predict the risks of developing intolerance in people in different populations with various socially significant diseases.says the clinical pharmacologist.

According to him, “you can’t just take and transfer foreign research to our population.” Taking into account racial and ethnic characteristics, they should be carried out exactly where the drugs are planned to be used.

– Here is one example: we studied the sensitivity of patients with cardiac pathology to one of the anticoagulants that affect blood clotting processes. In the European population, the pharmacogenetic marker associated with the safety of therapy (reduced risk of bleeding) was found in only 25-28% of people. And among the Mongoloid groups of Russia (Buryat, Nanai ethnic group) – 65-70%. This has never been described before.– notes the interlocutor of Izvestia.


Photo: TASS/Ivan Yudin

In his opinion, such nuances should be taken into account in methodological and national recommendations in order to ensure the safest and most effective use of drugs in our population, taking into account its ethnic and racial characteristics.

Wherein For a wider introduction of pharmacogenetics into practice, the doctor must understand how to interpret and use the test results when correcting the patient’s treatment. That is, in addition to conducting association studies, it is required to develop and automate algorithms for the use of pharmacogenetic markers, develop educational cycles and conduct educational events, and prepare reference materials for practicing physicians.

“For example, on the basis of our Department of Clinical Pharmacology and Therapy of the RMANPE, a cycle on clinical pharmacogenetics and the basics of personalized medicine is already operating, as well as the Russian Congress on Pharmacogenomics and the School of Young Scientists on Pharmacogenetics, Pharmacogenomics and Personalized Therapy,” concludes the interlocutor of Izvestia .

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