Despite the adoption of neoadjuvant FLOT chemotherapy as standard treatment for locally advanced gastric and gastroesophageal junction cancer, many patients fail to achieve meaningful pathological response, limiting efficacy. The aim of this study was to evaluate the impact of pharmacogenetic markers on pathological response in Russian patients receiving neoadjuvant FLOT. Thirty patients with locally advanced gastric or gastroesophageal junction adenocarcinoma received neoadjuvant FLOT followed by surgery. Polymorphisms in CYP3A5 (rs776746), CYP2C8 (rs10509681, rs11572080, rs1058930), ERCC1 (rs11615), and GSTP1 (rs1695) were analyzed. Favorable pathological response (TRG0-2) was observed in 23.3% of patients, including 3.3% complete responses. Most patients (76.7%) had minimal or no regression (TRG3-5). Clinical variables were not associated with response. ERCC1 (rs11615) showed a significant association: patients with the Wt/Wt genotype had higher odds of achieving TRG0-2 (OR = 8.889; p = 0.033; 95% CI: 1.294-61.058). No associations were found for CYP3A5, CYP2C8, or GSTP1. Median PFS was 18.21 months in TRG3-5, while not reached in TRG0-2 (p = 0.108). No significant PFS differences by ERCC1 genotype were observed (p = 0.525). ERCC1 (rs11615) may serve as a potential pharmacogenetic marker of response to FLOT, supporting further research in personalized treatment strategies.

Background/Objectives: Pharmacogenetic variability plays a crucial role in determining both the efficacy and toxicity of chemotherapy for gastrointestinal cancers. However, data on allele frequencies and their clinical relevance in Russian populations remain scarce. Methods: We conducted a prospective observational study of 412 patients with gastrointestinal malignancies between 2020 and 2023. Pharmacogenetic testing was performed prior to the initiation of chemotherapy using real-time allele-specific PCR and microarray hybridization technology. Polymorphisms in the DPYD, UGT1A1, CYP2C8, CYP3A5, GSTP1, ERCC1, XPC, CDA, MTHFR, TYMS, and SLC31A1 genes were analyzed. Results: The frequency of most variants was consistent with those reported in European populations, reflecting the ethnic proximity of the studied cohort. Several clinically relevant variants were identified: DPYD rs2297595 occurred more frequently than in European cohorts, and UGT1A1 rs8175347 was observed at a higher prevalence, underscoring the potential risk of irinotecan-related neutropenia and diarrhea. CYP2C8 rs10509681 was present at frequencies comparable to European populations and is associated with an increased risk of taxane-induced peripheral neuropathy. Other markers (GSTP1, ERCC1, CDA, SLC31A1, MTHFR, TYMS) demonstrated variable associations with chemotherapy efficacy and toxicity, consistent with findings from previous international studies. Conclusions: This study provides the first comprehensive description of pharmacogenetic polymorphisms in a Russian cohort of patients with gastrointestinal cancers. Our findings confirm the clinical importance of DPYD and UGT1A1 testing and highlight additional variants of potential interest.

Currently, the wide prevalence of the development of secondary to ACEIs cough (3.8 to 48 % based on different findings) is one of the core causes of the dramatic impairment of the patients’ quality of life, followed by drug discontinuation. The study had the purpose of revealing the pharmacogenetic predictors associated with the reduced risk of the dry cough AEs secondary to ACEIs, in particular enalapril. The study involved 217 patients with the diagnosis of "essential arterial hypertension", who took enalapril. The patients were assigned to 2 groups: Group 1 (study group): 104 patients without secondary to enalapril adverse drug reactions; and Group 2 (control group): 113 patients with secondary to enalapril cough. All the patients underwent pharmacogenetic testing. The analysis of the distribution of frequencies of the polymorphisms rs4149056 of gene SLCO1B1, rs4459610 of gene ACE, rs1799722 of gene BDKRB2, and rs62151109 of gene CLASP1 has revealed no differences between the group without adverse drug reactions and that with secondary to enalapril dry cough. The study has revealed a statistically significant association between the absence of adverse drug reactions and the presence of the genotype AG of gene SLCO1B1 rs2306283, genotype GG of gene ABO rs8176746 and rs495828.

Aim. The aim of our study was to investigate the influence of polymorphic markers of CYP3A4*22 CYP3A4*22 (c.522-191C>T, rs35599367), CYP3A5*3 (c.219237A>G, rs776746), ABCB1 rs1045642 (c.3435T>C) and rs4148738 (c.2692-2236C>T) genes on the plasma concentration of apixaban, on changes in prothrombin time (PT), activated partial thromboplastin time (APTT), and bleeding development in patients taking apixaban.Material and methods. The study included 108 patients with non-valvular atrial fibrillation and deep vein thrombosis receiving apixaban in therapeutic doses. Genotyping was performed by real-time polymerase chain reaction. Apixaban concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode. Because the daily dose of apixaban was different (5, 10, and 20 mg daily), the residual equilibrium concentration (Cmin,ss) of apixaban was adjusted relative to the daily drug dose (Cmin,ss/D). PT and APTT were determined using an automatic coagulometer analyzer Destiny Max (Tcoag, Ireland). Statistical processing was performed in SPSS Statistics 20.0 program.Results. We found that patients with CT ABCB1 (rs4148738) C>T genotype had higher Cmin,ss /D value than patients with TT genotype (6.23 [4;13] vs 5.77 [4;17], p=0.018). No statistically significant associations were found between carriage of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T gene polymorphisms and Cmin,ss /D value of apixaban. Also, there was no significant effect of carrying polymorphisms rs35599367, rs776746, rs4148738,rs4148642, and the above genes on the risks of hemorrhagic complications. However, the influence of ABCB1 (rs1045642) C>T polymorphism on the PT value was found (TT ABCB1 (rs1045642) C>T genotype carriers the CT value wassignificantly higher than in CT genotype (17.0 [40;112] vs. 14.9 [35;132]) p=0.044).Conclusion. It was found that the Cmin,ss /D value was higher in patients with CT ABCB1 (rs4148738) C>T genotype than in patients with TT genotype. At the same time, carriage of polymorphisms of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T genes did not affect the pharmacokinetics of apixaban and the risk of bleeding. We also identified the effect of ABCB1 (rs1045642) C>T gene polymorphism on the PT value.

BACKGROUND: Angioneurotic edema is the most dangerous complication in angiotensin-converting enzyme inhibitors (ACEIs) therapy. Based on the current data, the clinical and genetic predictors of angioedema development are still understudied, which demonstrates the relevance of this study. OBJECTIVE: To reveal the pharmacogenetic predictors of the angioedema as a secondary side effect to enalapril in patients with essential arterial hypertension. METHODS: The study enrolled 111 subjects randomized into two groups: study group, patients with the angioedema as a secondary side effect to enalapril; and control group, patients without adverse drug reaction. All patients underwent pharmacogenetic testing. RESULTS: An association between the development of the angioneurotic edema and the genotypes AA rs2306283 of gene SLCO1B1, TT rs4459610 of gene ACE, and CC rs1799722 of gene BDKRB2 in patients was revealed. CONCLUSION: The findings justify further investigations of the revealed genetic predictors of angioedema with larger-size patient populations.

Background. There is a mounting evidence in the scientific literature that susceptibility to SARS-CoV-2 infection could vary. The severity of COVID-19 symptoms can range from asymptomatic to severe respiratory failure, requiring prolonged artificial ventilation. The underlying causes of this range of clinical manifestations remain unclear. Identification of the risk factors that may cause this variation in clinical symptoms is important for identifying the most susceptible populations at highest risk. This should help improve prevention measures, reduce hospitalizations, and decrease the mortality rate of the disease. Previously, an association has been found between the severity of COVID-19 and the genetic markers rs11385942 G>GA and rs657152 A>C.The aim. To assess the impact of carrying polymorphic markers rs11385942 G>GA and rs657152 A>C on the severity of COVID-19 in patients undergoing specific therapy. Materials and methods. A total of 240 patients hospitalized with a coronavirus infection were included in the study. All patients received therapy with favipiravir or remdesivir. The presence of the rs11385942 G>GA and rs657152 A>C variants was determined in all patients. The study compared the length of hospital stays, frequency of patient transfers to the intensive care unit (ICU), and frequency of clinical outcomes (recovery or death) among carriers of allelic variants of the markers under investigation.Results. There were no significant associations between the carriage of variants rs11385942 G>GA and rs657152 A>C and the duration of patients’ hospitalization, frequency of patient transfers to the ICU, and patient outcomes.Conclusion. The carriage of rs11385942 G>GA and rs657152 A>C variants did not affect the severity or type of clinical outcomes in patients with COVID-19.

Background. The use of P-glycoprotein (P-gp) inhibitors and carriage of certain ABCB1 polymorphisms can lead to increased concentrations of rivaroxaban and the development of bleeding.The aim of the study. To study the features of drug-drug interactions (DDI) of rivaroxaban in patients over 80 years of age with non-valvular atrial fibrillation depending on the ABCB1 genotype (rs1045642 and rs4148738) using the example of verapamil (P-gp inhibitor) and amlodipine.Materials and methods. One hundred and twenty-eight patients were examined (median age – 87.5 [83–90] years). Genotyping, determination of the minimum equilibrium concentration of rivaroxaban (Cmin, ss), with standardization for the daily dose (Cmin, ss/D), coagulogram and analysis of medical documentation for the presence of clinically relevant non-major bleeding (CRNM) were carried out. Analysis of CRNM was performed depending on the ABCB1 genotype.Results. The use of rivaroxaban with verapamil in comparison with patients not taking calcium channel blockers (CCBs) leads to high Cmin, ss values in the CC genotype (rs1045642, rs4148738); Сmin, ss and Сmin, ss/D in the CT genotype (rs1045642); prothrombin time in the CC genotype (rs1045642), more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). In comparison with patients taking amlodipine, it leads to high Cmin, ss values in the CT genotype (rs1045642), a more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). The use of rivaroxaban with amlodipine in comparison with patients not taking CCBs leads to high Cmin, ss and Cmin, ss/D values in the CC genotype (rs1045642) (p < 0.017).Conclusion. The use of verapamil with rivaroxaban in ABCB1 TT carriers (rs4148738 and rs4148738) leads to the development of CRNM in 75 and 78 % of cases, respectively. In patients taking rivaroxaban, it is advisable to test the ABCB1 genotype (rs4148738 and rs4148738) before adding a P-gp inhibitor to therapy.

Abstract Objectives Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes of DNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients. Methods The study included 181 patients (37 men, 144 women; median age 56 [41; 66.3] years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. NFKB1, ATM, ATG16L2, ATG10, TGFB1, and TNF polymorphisms were determined by allele-specific realtime-PCR. Results The frequency of adverse reactions was the following: gastrointestinal symptoms – 57.9 %, local symptoms – 65.8 %, cerebral symptoms – 46.8 %, fatigue – 54.4 %; signs of sialoadenitis six months after radioiodine therapy – 25.2 %. TT genotype carriers of ATG10 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of ATG10 rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of TGFB1 rs1800469 (vs. AG+GG). CC genotype of ATG10 rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the ATM rs11212570 had a protective role against fatigue. TGFB1 rs1800469 was associated with signs of sialoadenitis six months after radioiodine therapy. Conclusions Genetic factors may contribute to the occurrence of adverse reactions of radioiodine therapy in thyroid cancer patients.

Introdiction . Systemic chemotherapy (CT) based on oxaliplatin, 5-fluorouracil, capecitabine is the standard of treatment for advanced gastric, colorectal and rectal cancer, which is characterized by frequent development of severe adverse events (AEs). The results of translational studies in the Russian patient population are limited, it is necessary to study pharmacogenetic markers. Aim. To study the frequency of carrying allelic variants of DPYD, GSTP1, MTHFR, XPC, ERCC1, TYMS genes and their association with the development of AEs during palliative treatment with FOLFOX/XELOX. Materials and methods . A total of 166 patients (67 gastric cancer, 99 colorectal cancer) were included in the prospective observational study. All patients underwent pharmacogenetic testing by hybridization analysis on biological microarrays ( DPYD (rs2297595 and rs75017182), MTHFR (rs1801133), XPC (rs2228001), TYMS (rs11280056), ERCC1 (rs3212986)) and PCR ( GSTP1 (rs1695), ERCC1 (rs11615)) before starting CT. The genotype frequency distribution was analyzed between the groups of patients with and without the development of severe AEs. Results . AEs developed in 97.7% of patients, severe AEs accounting for 54.2%. According to the results of univariate analysis, TC genotype of DPYD gene rs2297595 OR = 3.0 (95% CI 1.2–7.3, p = 0.025), GG genotype of GSTP1 gene rs1695 OR = 2.9 (95% CI 1.02–8.6, p = 0.038) were associated with the development of severe neutropenia. In multivariate analysis TT genotype rs2297595 of the DPYD gene remained the only predictor of severe neutropenia (B ± SE = -1.103 ± 0.503; DI [-2.090; -0.116]; p = 0.028). Conclusions . The results of this study allowed us to identify possible markers of toxicity of FOLFOX/XELOX chemotherapy.

Цель. Изучить ассоциации между носительством полиморфизмов генов NFKB1, ATM, ATG16L2 и ATG10 иразвитием резистентности к радиойодтерапии, возникновением нежелательных реакций у больных раком щитовидной железы.

Angiotensin-converting enzyme inhibitors (ACEIs) are among the most prescribed and effective medicinal products for the treatment of several cardiovascular diseases. According to a number of studies, 30% of patients taking ACEIs develop adverse drug reactions (ADRs), and treatment discontinuation is often required as a result. The most common ADR associated with ACEIs is a dry (non-productive) cough. Nevertheless, the clinical signs and medical history predictive of this ADR in cardiovascular patients are still understudied. The aim of the study was to analyse the clinical signs and medical history predictive of cough in patients with cardiovascular conditions treated with enalapril. Materials and methods. The study was carried out in 2019–2022 and enrolled 224 patients with essential hypertension (grades 2 and 3) treated with enalapril at a dose of 10–20 mg/day. The patients were assigned to 2 groups: Group 1 included 113 patients with enalapril-associated cough, while Group 2 (control group) comprised 104 patients without this ADR. At screening, all the patients underwent a general examination and a check of their allergy and medication history. Using the data obtained, the authors analysed the association of the clinical signs and medical history with the ADR of interest (dry cough). Results. In contrast to the control group, the group with ACEI-associated dry cough included more patients with a history of drug-induced toxicoderma (OR=5.639, CI 2.234–14.236, χ 2 =15.845, and p <0.001) or type 2 diabetes mellitus (OR=3.409, CI 1.461–7.953, χ 2 =8.7472, and p <0.01), a family history of bronchial asthma (OR=4.141, CI 2.066–8.299, χ 2 =17.417, and p <0.001), and a close family history of severe allergic reactions (OR=3.714, CI 1.720– 8.018, χ 2 =12.137, and p <0.001). Conclusions. A family history of allergy increases the probability of dry cough in patients taking ACEIs. In order to improve the safety of ACEI therapy, patients with cardiovascular conditions should be asked more detailed questions about their personal or first-degree family history of allergy.

Background. Previously, genetic markers rs11385942 G>GA and rs657152 C>A of disease severity were identified for COVID-19. The study of the prevalence of clinically significant genetic markers may be useful for the development of region-specific approaches to disease control, considering, among other things, the ethnic composition of the territory, which is especially relevant for Russia. Based on the ethnic heterogeneity of the population of the Republic of Dagestan, this region was chosen as an example to study the distribution of COVID-19 severity markers of interest. Objective. Investigation of the prevalence of rs11385942 G>GA and rs657152 C>A markers among five ethnic groups residing in Dagestan. Methods. The study included 605 healthy volunteers (158 men and 447 women) from five different autochthonous ethnic groups living in the Republic of Dagestan: 118 Avars, 121 Dargins, 116 Laks, 127 Kumyks, and 123 Lezgins. Blood served as a material for determining polymorphisms. Carriage of polymorphic markers was determined by real-time polymerase chain reaction method. Results. The prevalence of rs11385942 G>GA marker ranges from 10.17% among Avars to 15.04% among Lezgins; significant differences were found in comparison with Russian ethnic group from literature sources. The second marker – rs657152 A>C — is distributed relatively homogeneously in the studied groups, without significant differences, and correlates with the data on the frequency of marker detection among Russians, as well as among European populations and worldwide — 50–60%. Conclusion. No differences were found within the ethnic groups of Dagestan in the carriage of both studied COVID-19 severity markers. At the same time, the rs11385942 G>GA marker detection frequency in the analyzed groups was on average higher in comparison with Russians and the average values for European populations.

Introduction . An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery. Aim . To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy. Materials and methods . A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0. Results . There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels). Conclusion . In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed.

Abstract Objectives Development of the secondary to ACEI cough leads to discontinuation of the drugs of this group. Assessing the safety of the ACEIs with further development of customized approaches for their administration is a major scientific and practical problem. The objective of this study was to assess the association of the genetic markers with the development of the adverse drug reaction in the form of secondary to enalapril dry cough in the patients with essential arterial hypertension. Methods Study involved 113 patients with the secondary to enalapril cough and 104 patients without development of the secondary to enalapril adverse drug reaction. Results The patients carriers of the genotype AA rs2306283 of gene SLCO1B1 had 2-fold higher odds of developing the dry cough than those with the genotypes AG and GG (ОR=2.01, 95%CI=1.10–3.66, р=0.023). Similarly, the patients heterozygous for rs8176746 of gene АВО had 2.3-fold higher odds of developing the ADR in the form of dry cough than the carriers of the genotypes GG and TT (ОR=2.30, 95%CI=1.24–4.29, р=0.008). Conclusions Statistically significant association between the development of the ADR in the form of secondary to enalapril dry cough and polymorphisms rs2306283 of gene SLCO1B1 and rs8176746 of gene ABO was revealed.

Electroporation can be used as a nonthermal method to ablate myocardial tissue. However, like with all electrical ablation methods, determination of the energy supplied into the myocardium enhances the clinically required controllability over lesion creation.To investigate the relationship between the magnitude of epicardial electroporation ablation and the lesion size using an electrically isolating linear suction device.In 5 pigs (60–75 kg), the pericardium was opened after medial sternotomy. A custom linear suction device with a single 35 × 6–mm electrode inside a 42-mm-long and 7-mm-wide plastic suction cup was used for electroporation ablation. Single cathodal applications of 30, 100, or 300 J were delivered randomly at 3 different epicardial left ventricular sites. Coronary angiography was performed before ablation, immediately after ablation, and after 3 months survival. Lesion size was measured histologically after euthanization.The mean depth of 30, 100, and 300 J lesions was 3.2 ± 0.7, 6.3 ± 1.8, and 8.0 ± 1.5 mm, respectively (P = .0003). The mean width of 30, 100, and 300 J lesions was 10.1 ± 0.8, 15.1 ± 1.5, and 17.1 ± 1.3 mm, respectively (P<.0001). Significant tissue shrinkage was observed at the higher energy levels. No luminal arterial narrowing was observed after 3 months: 2.3 ± 0.3 mm vs 2.3 ± 0.4 mm (P = .85).The relationship between the amount of electroporation energy delivered through a linear suction device with a single linear electrode and the mean myocardial lesion size is significant in the absence of major adverse events or permanent damage to the coronary arteries.

ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial. To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF). 128 patients aged 80 years and older (median [Me] age 87.5 [83.0–90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (Cmin,ss) of rivaroxaban and prothrombin time (PT) and analyzed prior medical records for clinically relevant non-major bleeding (CRNMB). CC genotype carriers had no differences in Cmin,ss (p > 0.05) compared with the CT and TT rs1045642 and rs4148738 genotypes carriers. CC genotype carriers had no differences in PT (p > 0.05) compared with the CT rs1045642 and rs4148738 and TT rs4148738 genotypes carriers. In the TT genotype PT levels were higher than in the CC rs1045642 genotype: Me 14.2 [13.0–16.1] sec vs 13.3 [12.4–14.5] sec (p = 0.049). Incidence of CRNMB was higher in patients with the TT genotype compared with the CC rs1045642 (29.3% vs 4.5%, p = 0.021) and rs4148738 (39.3% vs 8.1%, p = 0.008) and the CT genotype rs4148738 (39.3% vs 14.3%, p = 0.002). ABCB1 (rs1045642 and rs4148738) polymorphisms didn’t influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT–TT haplotype was associated with a higher frequency of CRNMB.

Objective The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation. Methods In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records. Results The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban. Conclusion Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug–drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.

Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients. Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients. Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.515.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan kits. Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04. Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.

The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) may be determined by the polymorphic nature of the CYP2C8, PTGS1 and PTGS2 genes.Objective: to analyze the nature of the distribution of CYP2C8*3 (rs10509681), CYP2C8*3 (rs11572080), PTGS1 (rs10306135), PTGS1 (rs12353214) and PTGS2 (rs20417) among residents of the North Caucasus.Patients and methods. The study involved 676 volunteers from Russian, Balkar, Kabardian and Ossetian ethnic groups. Carriage of polymorphic markers CYP2C8, PTGS1 and PTGS2 was determined using real-time polymerase chain reaction.Results and discussion. There were no significant differences between the groups in the rs10509681 and rs11572080 variants of the CYP2C8 gene. In all groups, the carriage of a combination of CYP2C8 and CYP2C9 alleles, encoding the phenotype of normal metabolizers, prevailed with a frequency of about 75% or more. The rs10306135 variant of the PTGS1 gene was found in 5.9% of Russians, 1.1% of Balkars, 5.3% of Kabardians, and 10.6% of Ossetians; variant rs12353214 – in 19.1; 9.4; 10.8 and 9.2%, rs20417 polymorphism of the PTGS2 gene in 0.4; 5; 2.8 and 3.1% respectively.Conclusion. The data obtained can be used to develop a more rational approach to the prescription of NSAIDs, taking into account the genetic characteristics of the local population in ethnic regions.

AIM To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain. MATERIALS AND METHODS The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool GTT). RESULTS According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups. CONCLUSION In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.