Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

Мирзаев, К. Б.; Fedorinov, Denis S.; Ivashchenko, Dmitriy V.; Сычев, Д. А.

doi:10.20996/1819-6446-2019-15-3-393-406

Cited by 17 publications

(1 citation statement)

References 64 publications

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“…Знание геногеографии клинически значимых биомаркеров позволяет выделять популяции, для которых проведение фармакогенетического тестирования (ФГТ) будет приоритетным и обоснованным; такой подход исключит необоснованное назначение ФГТ для всех пациентов. Во многих работах показано, что для народонаселения России характерна значительная этно-региональная изменчивость частот фармакогенетических маркеров [8][9][10][11][12][13][14], что приводит к необходимости адаптации фармакогенетических рекомендаций к конкретным популяциям и народам. Для выявления биомаркеров, требующих наибольшей адаптации ФГТ из-за значительных различий между популяциями, полезно использовать такой инструмент, как выявление эффектов отбора.…”

Section: Introductionunclassified

Genogeographic technologies of a population biobank as a tool for assessing selection effects (using the example of pharmacogenetic biomarkers of cardiovascular diseases)

Balanovskaya,

Gorin,

Ponomarev

et al. 2023

Cardiovasc Ther Prev

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Significant differences between the gene pools of Russian peoples require the development of ethno- regional adapted pharmacogenetic tests and the identification of priority regions for their implementation.Aim. To develop a genogeographic technology to identify selection effects using the example of biomarkers that are significant for pharmacotherapy of patients with cardiovascular diseases (CVD), using a population biobank and the Pharmacogenetics of Populations of Russia and Adjacent Countries database.Material and methods. Deoxyribonucleic acid (DNA) samples from the Biobank of Northern Eurasia from 20 metapopulations of the indigenous population of the European Russia were studied using two following data sets: 24 pharmacogenetic markers of CVDs (3170 samples); 1 276 191 polymorphic DNA markers of the autosomal genome (1293 samples). For each data set, estimates of interpopulation variability in the gene pool are provided — the difference between these estimates characterizes the selection pressure on each of the 24 CVD biomarkers. A genogeographic atlas has been created, the maps of which demonstrate the selection pressure on each biomarker according to the degree of deviation from the selective- neutral variability of the gene pool.Results. Twenty-four CVD biomarkers are divided into three following classes: those close to selective- neutral variability, those subject to stabilizing and differentiating selection. For each of the 24 CVD biomarkers, genogeographic maps were created that reveal selection effects in each of the 20 metapopulations. Most maps have identified populations that are under differential selection pressure and therefore a priority for the implementation of ethno- regionally adapted pharmacogenetic protocols.Conclusion. Pharmacogenetic markers and populations under differential selection require the development of ethno- regionally adapted pharmacogenetic tests. The created cartographic atlas of selection can serve as the basis for pharmacogenetic studies carried out using genogeographic methods.

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Section: Introductionunclassified

Genogeographic technologies of a population biobank as a tool for assessing selection effects (using the example of pharmacogenetic biomarkers of cardiovascular diseases)

Balanovskaya,

Gorin,

Ponomarev

et al. 2023

Cardiovasc Ther Prev

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The clinical aspects ot the sulphonylurea compounds from the position of the cardioprotective approach at patient with type 2 diabetes, using glucocardiomonitoring

et al. 2022

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BACKGRAUND: Now the trend of Type 2 Diabetes Mellitus (T2DM) management from glucocentric to cardioprotective approach take place, and it especially relevant for the multiple group of patients with T2DM using Sulphonylurea (SU). Meanwhile the synchronized glucocardiomonitoring allowed to providing the accurate information about the cardiometabolic status of patients with T2DM.AIMS: Using the professional glucocardiomonitoring for T2DM-SU patients to investigate the relation between the glycemic variability, integral glycemic parameters and proarrhythmogenic cardiovascular events and the long-term cardiovascular outcomes.MATERIALS AND METHODS: In the observational (randomised for inclusion of patients) controlled trial the SU-patients with the T2DM duration 9,8±6,6 years were included, whom the professional glucocardiomonitoring had been made during 5 days and then the fatal and non-fatal cardiovascular events had been investigated during 5 years. RESULTS: From 283 patients with T2DM 154 patients (the basic group) used gliclazide (original drug Diabeton MB), 129 patients (the control group) used glibenclamide. The relation between the rising of the glycemic variability and cardiovascular events (the prolongation QT interval, the ST depression (dST), ventricular arrhythmias (VAs)) were demonstrated. At the basic and the control groups the coefficient of variation (CV) was 23,0±8,1 and 30,1±10,7% respectively (p<0,001), TIR-HYPO — 0,8±2,4 and 3,5±5,4% (p<0,001), the number of glycemia differences > 4 mmol/L/hr — 2,3±3,6 and 3,5±4,3 (p=0,010), the minimal glycemia level — 4,6±1,0 and 3,9±1,4 mmol/L (p=0,001). The followed differences of cardiovascular parameters were determined: QTc — 412±24 and 423±28 ms (p=0,001), dST — 0,052 [0; 0,275] and 0,109 [0; 0,422] (ratio, p=0,012), VAs — 2,2 [0; 5,9] and 3,5 [0; 8,3] (cases/pts, p=0,008). The long-term cardiovascular outcomes from the gliclazide and glibenclamide therapy (cases/100 pts-years): the total and cardiovascular death — 0,12 [0; 1,74] and 0,76 [0; 4,62] (p=0,062), cardiovascular death -0,12 [0; 1,74] and 0,62 [0; 4,08] (p=0,122), myocardial infarction — 1,56 [0; 6,94] and 2,00 [0; 8,02] (p=0,193), stroke — 0,78 [0; 4,66] and 0,76 [0; 4,62] (p=0,169), chronic heart failure — 0,52 [0; 3,72] and 1,24 [0; 6,06] (p=0,095), MACE — 2,46 [0; 10,1] и 2,62 [0; 9,38] (p=0,095), severe hypoglycemia at home — 2,46 [0; 9,12] и 7,24 [0; 16,68] (p<0,001).CONCLUSIONS: It was demonstrated that the gliclazide (original drug Diabeton MB) administration is characterized with the better quality of glycemia control, the lower glycemic variability, the lower frequency of the SU-associated hypoglycemia, dST, VAs, the lower prolongation QTc interval. The implementation of the synchronized glucocardiomonitoring is necessary for minimization of the cardiovascular T2DM-complications and for the choice of the personalized

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Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen

Сычев

Морозова

Shatskiy

et al. 2022

Drug Metabolism and Personalized Therapy

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Objectives Patients undergoing cardiac surgery develop post-sternotomy pain syndrome. The aim of this study was evaluation of the influence of CYP2C9, PTGS-1 and PTGS-2 genes polymorphisms on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery. Methods The study included 90 patients undergoing cardiac surgery. A real-time polymerase chain reaction was used for the detection of single nucleotide polymorphisms (SNP). Pain intensity was measured by the Numeric Rating Scale (NRS). Dyspeptic symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Acute kidney injury (AKI) was determined by Kidney Disease Improving Global Outcomes criteria. Results Pain intensity by the NRS score was significantly higher in patients with CYP2C9*3 АA genotype compared to АC genotype: 7 [1,10] and 6 [2,7] (p=0.003); 7 [1,10] and 6 [2,7] (p=0.04); 6 [0; 10] and 5 [2,6] (p=0.04); 5 [0; 8] and 3 [0; 8] (p=0.02), on days 1, 2, 3 and 5 in the postoperative period, respectively. GSRS score was higher in patients with CYP2C9*2 CT genotype compared to CС genotype: 19 [15; 42] and 18 [15,36] (p=0.04), respectively. There were no significant differences in the pain intensity, dyspepsia severity and AKI frequency in patients with homozygous and heterozygous genotypes for PTGS-1 rs10306135, PTGS-1 rs12353214, PTGS-2 rs20417. Conclusions CYP2C9*3 and CYP2C9*2 gene polymorphisms may affect efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

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Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

Cited by 17 publications

References 64 publications

Genogeographic technologies of a population biobank as a tool for assessing selection effects (using the example of pharmacogenetic biomarkers of cardiovascular diseases)

Genogeographic technologies of a population biobank as a tool for assessing selection effects (using the example of pharmacogenetic biomarkers of cardiovascular diseases)

The clinical aspects ot the sulphonylurea compounds from the position of the cardioprotective approach at patient with type 2 diabetes, using glucocardiomonitoring

Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen

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