Pharmacogenetics (PG) as an independent discipline originated in the late 1950s. The term was proposed by German scientist Friedrich Vogel in 1957, and in 1962 the fundamental work by W. Kalow "Pharmacogenetics: Heredity and Response to Drugs" was published.

The antithrombotic drug Warfarin showed a phenomenal result in personalizing dosing using PG. It seems this was a "survivorship bias" or a perfect exception to the rule. For other drugs, it did not work as well. Decades have passed since the completion of the Human Genome Project, and we have the opportunity to use available data to find all associations.

The PG approach for dosing in the USA includes 132 drugs, in the European Union 37 drugs, in Russia they promise only 11 drugs by 2030. (There is a caveat that this article does not consider PG in oncology. About 30 drugs by my count).

Let us ask ourselves why there is still no widespread implementation of pharmacogenetics?

First of all, due to gaps in standardized dosing recommendations, complex interactions of multiple genes/drugs, and lack of confidence among physicians. We can read the DNA sequence, identify genetic variants of important enzymes that affect drug action. But a clear translation into dosing recommendations has not appeared. There is a lack of data on enzyme activity rates for different genetic variants.

Enzymes (CYPs) are not the only ones and should not determine the individual patient response to therapy. Now we can search for genetic factors across the entire genome without explaining how the absorption-transport and metabolism systems of each drug "should" work. Nevertheless, such genome-wide studies of drug action have not been conducted in Russia.

There is no open Russian biobank with known documented response to drug therapy. Physicians and patients do not record or report adverse effects. And the pharmacovigilance service does not provide data to researchers. Consequently, such a multinational country is forced to use the achievements of other countries.

The generally low quality of fundamental research conducted in Russia. This includes limited patient samples, multiple concurrently used drugs. Here we can also note the lobbying of drug manufacturers and laboratory test systems; they pay (sometimes) for research and influence the design and choice of methods.

For comparison, the scale in the European Union: a genetic study of schizophrenia including more than 37,000 people with schizophrenia and 113,000 control subjects...

Resistance of physicians to progress. A global problem is the difficulty of training physicians, lack of time for quality education. There is a habit of using past experience (and positive reinforcement from pharmaceutical companies).

Conclusion: Pharmacogenetics is a complex technology, and quick and cheap implementation has not been achieved. Systemic solutions are needed. At least, transfer the experience of other countries regarding a hundred drugs that have proven economic benefits.

Meanwhile, Sechenov Academy has developed a pharmacogenetic approach for personalized selection of drugs for the treatment of hypertension. Comment by the Public News Service

@drakarasev