Relevance. Methotrexate (MT) is the most prescribed baseline anti-inflammatory drug for the treatment of rheumatoid arthritis (RA). The reason for withdrawal of the drug is mostly because of its ineffectiveness, which is determined by the genetic characteristics of patients. Predicting the response to MT remains an urgent task in practical medicine.

Objective. To evaluate the influence of single-nucleotide polymorphisms of ATIC, AMPD1, ADA and ITPA genes on MT efficacy in RA.

Materials and methods. The study group included patients with a reliable diagnosis of RA who received MT. After 6 months of therapy, the efficacy was monitored by the dynamics of the DAS28 index (Disease Activity Score). Genotyping of polymorphisms rs2372536 (C347G), rs244076 (T>C), rs17602729 (C34T), and rs1127354 (C94A) was performed by real-time polymerase chain reaction. Allele and genotype distribution frequencies of polymorphisms in patients with different MT efficacy levels were analyzed. To assess the reliability (p) of differences, χ2 was used. The strength of association of traits was evaluated by the odds ratio (OR).

Results. The C allele of the ATIC rs2372536 polymorphism was predominant in responders: 230 (68 %) versus the G allele 110 (32 %) (p = 0.073, OR [95% CI] 0.7 [0.5; 1.0] at the trend level. The frequency of occurrence of the CC genotype of ATIC rs2372536 was significantly higher in responders 80 (47%) than in non-responders 41 (33 %) (p = 0.016, OR = 0.6 [0.3; 0.9]. At the same time, the CG genotype was significantly more prevalent in non-responders 68 (55 %) than in responders 70 (41%) (р = 0.021, OR = 1.7 [1.09; 2.8]. The TC genotype of the ADA rs244076 polymorphism was more frequent at the trend level in non-responders 33 (27 %) versus 33 (18 %) in responders (p = 0.064, OR = 1.7 [0.9; 2.9]. There was no difference in the genotype and allele distribution of ITPA rs1127354 and AMPD1 rs 17602729 polymorphisms between responders and non-responders. The CG genotype of the ATIC rs2372536 polymorphism was associated with the response to MT in codominant and superdominant inheritance models: CG vs. GG, p = 0.042, OR = 1.9 [1.15; 3.13]; CG vs. CC + GG, p = 0.02, OR = 1.73 [1.09; 2.77], respectively. In the dominant model, CG + GG vs. CC genotypes were predominant in responders: p = 0.016, OR = 1.80 [1.11; 2.91]. The dominant model of inheritance was the most significant, with the lowest Akaike information criterion value of 398.5. The data indicate a trend toward a higher frequency of the TC genotype of the ADA rs244076 polymorphism in responders in the super dominant model: TC vs. TT + CC, p = 0.066, OR = 1.69 [0.97; 2.96].

Conclusion. MT efficacy is associated with ATIC rs2372536 and ADA rs 244076 polymorphisms. Single-nucleotide polymorphisms ITPA rs1127354 and AMPD1 rs17602729 do not independently contribute to the therapeutic efficacy of MT in patients with RA. The dominant inheritance pattern of the ATIC rs2372536 gene is the most significant for predicting the efficacy of MT therapy in RA.

Relevance. The scale of use of acetylsalicylic acid is determined by its use as a means of suppressing platelet aggregation in patients with coronary heart disease. It has been established that the antiplatelet effect in some patients may be weak and insufficient to prevent thrombosis. In this regard, the problem of resistance to acetylsalicylic acid requires more detailed study.

Objective. To study the influence of acetylsalicylic acid on aggregometry indicators in men with the same body weight, belonging to the Russian and Armenian ethnic groups of residents of the Stavropol Territory, who were treated in a specialized hospital.

Material and methods. Men who were treated in the following hospital departments were examined: cardiology department; department of acute coronary syndrome, and department of acute cerebrovascular accidents. Russian ethnic group — 53, Armenian — 24 patients. When forming groups, a body mass index in the range of 33.0±3.9 was considered to be selected patients with similar body weight. Patients received 75 or 100 mg of acetylsalicylic acid per day. In the department of acute coronary syndrome, acetylsalicylic acid was used along with clopidogrel — 75 mg per day. Aggregatometry was performed after 5 days of regular antiplatelet therapy.

Results. In men of the Russian ethnic group who received acetylsalicylic acid at a daily dose of 75 mg, the amplitude of ADP-induced aggregation was statistically significantly higher (Me=13.9 %) than in the Armenian group (Me = 3.0) (p = 0.024). Armenians showed smaller amplitudes of aggregation during induction with ristomycin (33.3 %) than Russians (52.7 %). When using acetylsalicylic acid at a higher dose (100 mg per day), as well as when prescribing two antiplatelet agents, the differences between ethnic groups decreased.

Conclusion. When using acetylsalicylic acid at a dose of 75 mg/day in sick men of the Russian ethnic group, insufficient antiplatelet activity of the drug can be expected.

Relevance. Antipsychotics are widely used in psychiatry. Haloperidol remains one of the most commonly used antipsychotics because of its effectiveness. However, it has various adverse reactions, including an increased risk of QT prolongation, a potentially fatal complication that can lead to Torsade de Pointes and sudden cardiac death.

Objective. To systematize information for practicing psychiatrists and clinical pharmacologists regarding a personalized approach to the prevention of QT interval prolongation in patients with mental disorders who are taking haloperidol.

Methods. A search for full-text articles published from 02/01/2013 to 02/01/2024 was conducted using PubMed, eLIBRARY.RU, and Google Scholar.

Results. This short review analyzes and summarizes the results of foreign and domestic studies on the effect of haloperidol on the QT interval, the role of risk factors and hereditary predisposition in the development of haloperidol-induced prolongation of the QT interval, and Torsade de Pointes in patients with mental disorders. The main mechanism of the cardiotoxic effect of haloperidol is the dose-dependent inhibition of potassium channels in the cardiomyocyte membrane. Haloperidol is extensively metabolized in the liver, which may cause significant interindividual variability in its pharmacokinetics. A decrease in the metabolism rate of haloperidol may lead to an increase in its concentration in the blood, thereby increasing the risk of developing cardiotoxic adverse reactions. To reduce the risk of developing haloperidol-induced prolongation of the QT interval, it is advisable to use predictive pharmacogenetic testing.

Conclusion. Generalized data on the effect of haloperidol on the duration of the QT interval and the risk of developing TdP in patients with mental disorders may be required by psychiatrists and clinical pharmacologists when selecting the dose and duration of haloperidol administration. Predictive pharmacogenetic testing can help reduce the incidence of potentially fatal cardiotoxic adverse reactions.

Relevance. Modern chemotherapy for Hodgkin lymphoma (HL) achieves long-term remissions in 80–85 % of patients. Some patients develop drugrelated toxicity. Polymorphisms in drug-metabolizing cytochrome P450 (CYP) genes contribute to individual differences in the therapeutic and side effects of chemotherapy. In this regard, chemotherapy for HL in Russia has not been sufficiently studied.

Objective. To study the relationship between polymorphic variants of CYP3A4, CYP3A5, CYP1A1, and CYP2B6 and the development of organotoxic effects of HL therapy.

Methods. Polymorphic variants CYP3A4 (rs4987161, rs28371759, rs2740574), CYP3A5 rs776746, CYP1A1 (rs1048943, rs4646421), and CYP2B6 (rs2279343) were determined by polymerase chain reaction with real-time detection. Their association with organotoxic complications was assessed by odds ratio and using Multifactorial Dimensionality Reduction (MDR).

Results. MDR analysis showed the significance of polymorphic variants of four genes for hepatotoxicity with the main contribution of CYP1A1 rs464642. Synergism was observed for CYP1A1 rs4646421 and CYP2B6 rs227934 and CYP2B6 rs227934 and CYP3A5 rs776746, and antagonism was observed for CYP1A1 rs4646421 and CYP3A5 rs776746. The main contributor to cardiotoxicity was CYP2B6 rs227934, which showed synergy with both CYP1A1 variants. The main contribution to the development of anemia was made by CYP3A5 rs776746, for which synergism with CYP1A1 rs104894 was noted; for leukopenia — CYP1A1 rs464642; for granulocytopenia — CYP2B6 rs227934, antagonism with CYP1A1 variants was noted; for thrombocytopenia — CYP3A4 rs2740574, antagonism with CYP3A5 rs776746 was observed.

Conclusion. The results show that different combinations of polymorphic variants of CYP genes are associated with different types of organotoxicity and that different genes make a major contribution.

The introduction of genetics into medicine has unlocked the ability to predict drug efficacy and/or toxicity, and pharmacogenomics makes an important contribution to personalized medicine and pharmacotherapy. Pharmacogenetic testing identifies genetic variants that alter the response to a drug. At the same time, up to 95 % of the population is a carrier of at least one genetic variant; however, a patient may be a carrier of several genetic variants at the same time, which may be important not only in cases of prescription of a particular drug but also of other drugs during the future life. In this regard, two pharmacogenetic approaches are relevant — reactive or preventive testing. The current trend is pharmacogenetic panel testing as a model for precision medicine. In a multiplex panel model, several gene variants affecting drug response are tested simultaneously, and the data are stored for future use.

However, practicing physicians have difficulty with genetic information because of low awareness of pharmacogenomics or lack of proper infrastructure and IT tools. Despite the publication of pharmacogenomics guidelines in the US (CPIC) and in the European Union (DPWG), most patients are still treated according to standard clinical practice. It was strategically important to establish interdisciplinary working groups — pharmacogenomics consortia — in the USA and the European Union, the purpose of which is to introduce pharmacogenetics into widespread clinical practice. The activities of these consortia and the results achieved are presented. In the work of consortia, various studies are used to analyze the level of knowledge on pharmacogenomics, application of pharmacogenetic testing, and clinical results, including different methodological approaches. The foreign experience (USA, European Union, China) in the dissemination and implementation of pharmacogenomics in real clinical practice is presented.