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.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a fivefold increase in stroke risk. Direct oral anticoagulants (DOACs), including apixaban, are now the preferred therapy for stroke prevention in patients with non-valvular AF (NVAF). However, interindividual variability in drug response and safety remains a major challenge, particularly in elderly patients with comorbidities and polypharmacy. Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to variability in apixaban exposure and bleeding risk. This study aimed to evaluate the association of polymorphisms in ABCB1, CYP3A4, and CYP3A5 with steady-state plasma concentrations of apixaban (Cssmin) and hemorrhagic complications in elderly patients with NVAF. Methods: This cross-sectional study included 197 patients (mean age 83 ± 8 years; 67% women) with NVAF treated with apixaban (5 mg twice daily). Genotyping of ABCB1 (rs1045642, rs2032582, rs1128503), CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746) was performed using allele-specific real-time PCR. Cssmin of apixaban was determined by high-performance liquid chromatography coupled with tandem mass spectrometry. Associations with bleeding events were evaluated. Results: Bleeding events were recorded in 40 patients (20.3%). An association signal was observed for ABCB1 rs1045642, where carriers of the CC genotype had a higher risk of bleeding compared with alternative alleles (OR = 2.805; 95% CI: 1.326–5.935; p = 0.006). After correction for multiple testing, the association remained significant only under the log-additive model (OR = 1.93 per C allele; 95% CI: 1.17–3.20; q = 0.0275; p_adj = 0.044), while recessive and codominant effects did not withstand Bonferroni adjustment. No significant associations were observed for rs2032582, rs1128503, CYP3A4*22, or CYP3A5*3. None of the studied polymorphisms, including rs1045642, significantly affected Cssmin. Concomitant therapy, particularly with antiarrhythmic drugs and statins (rosuvastatin), also increased bleeding risk. Conclusions: The findings highlight the potential contribution of ABCB1 rs1045642 and specific drug–drug interactions to the risk of hemorrhagic complications in elderly NVAF patients receiving apixaban.

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.

Aim. To conduct a comparative assessment of the short-term prognosis in patients with ST-segment elevation acute coronary syndrome (STE-ACS) without percutaneous coronary intervention (PCI) based on the Global Registry of Acute Cardiac Events (GRACE), Thrombolysis In Myocardial Infarction (TIMI), RECORD, PREdicting risk of Death In Cardiac disease Tool (PREDICT) scales and to ident ify the most significant markers of fatal and non-fatal complications.Material and methods. Eighty-two STE-ACS patients without PCI were examined. Risk assessment was carried out using the GRACE, TIMI, RECORD, and PREDICT scales. Outcomes were assessed 30 days after markers. To assess the predictive value of above scales, sensitivity (Se) and specificity (Sp), as well as relative risk with a 95% confidence interval, were calculated.Results. Comparative analysis of the prognosis of developing fatal complications in STE-ACS patients without PCI revealed the following predictive characteristics of scales: GRAСE — Se=1,000, Sp=0,54, χ²=25,763 (p<0,001); PREDICT — Se=0,281, Sp=0,96, χ²=20,297 (p<0,001); TIMI — Se=0,75, Sp=0,94, χ²=51,985 (p<0,001); RECORD — Se=1,000, Sp=0,48, χ²=21,716 (p<0,001). Regarding the development of non-fatal complications, the following data was obtained: GRACE — Se=0,680, Sp=0,760, χ²=9,970 (p0,05); TIMI — Se=0,120, Sp=1,000, χ²=8,171 (р<0,05); RECORD — Se=0,680, Sp=0,640, χ²=5,128 (р<0,05). The most significant criteria for developing fatal and non-fatal complications were identified as follows: Killip class II acute heart failure, systolic blood pressure 65 years, stage ≥II A chronic heart failure, ST elevation ≥1 mm at admission, ejection fraction ≤<40%.Conclusion. A comparative evaluation of the 30-day prognostic significance of short-term scales (GRACE, RECORD, TIMI, PREDICT) in STE-ACS patients without PCI showed an ambiguous prognosis for developing both fatal and non-fatal complications. High sensitivity rates for predicting fatal complications were revealed in the GRACE and RECORD scales (100 and 100%, respectively) relative to the TIMI and PREDICT (75 and 28,1%, respectively), as well as for non-fatal complications in the GRACE and RECORD (68% for both) scales relative to the TIMI and PREDICT (12 and 8%, respectively).

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.

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.