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Variants of the UGT1A1 gene are associated with impaired bilirubin metabolism, which is clinically expressed in Gilbert's syndrome (GS), Crigler-Najjar syndrome types I and II, as well as increased toxicity intaking certain drugs (indinavir, irinotecan, atazanavir, sorafenib, tocilizumab, belinostat, and paracetamol). A common manifestation of these conditions is unconjugated hyperbilirubinemia. The most common variant in the UGT1A1 gene associated with GS (the most common pathology caused by UGT1A1 gene variants) is the UGT1A1*28 variant, which is an increased number of TA repeats in the promoter of the UGT1A1 gene up to 7. However, the UGT1A1*28 variant is not the only gene variant capable of causing unconjugated hyperbilirubinemia. It is known that the variants UGT1A*7, UGT1A*6, and UGT1A*27 were found in the Asian population, which also causes GS with a high frequency. For Caucasians, the UGT1A1*28 variant remains the only common variant that causes GS. At the same time, even the carriage of the UGT1A1*28 variant in the homozygous state does not always lead to the appearance of clinical symptoms. While in the heterozygous form of the UGT1A1*28 variant, high unconjugated hyperbilirubinemia can be observed. Thus, other molecular genetic markers probably explain the incomplete penetrance and variable expressivity of the clinical manifestations of the UGT1A1 gene variants

Objective: to study the association of the G-174C (rs1800795) polymorphism of the IL-6 gene with depression in an open population of 25–44 year old in Novosibirsk.Patients and methods. In 2013–2016 years we examined 403 men (mean age – 34±0.4 years, response – 71%) and 531 women (mean age – 35±0.4 years, response – 72%) from an open population of 25–44 year old residents of the Oktyabrsky district, Novosibirsk, the sample was representative. Depression was assessed using the MONICA-MOPSY psychosocial questionnaire. Genotyping of the studied gene polymorphisms was carried out in the Laboratory of Molecular Genetic Research of Scientific Research Institute for Therapy and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk.Results and discussion. A severe level of depression occurred in 12.8% of the population, among men – in 8.9%, among women – in 15.8%; and moderate level – in 24.5% of the population (among men – 21.3%, among women – 26.9%). The most common in the population was the heterozygous C/G genotype (45.1%), the G/G genotype was observed in 34.6% of the population and, finally, C/C in 20.3% of participants. The most common allele of the IL-6 gene of the G-174C polymorphism (rs1800795) was the G allele in 57.5% of the population, and the C allele in only 42.5%. Among carriers of the G/G genotype of the IL-6 gene, a moderate (39.7%) or severe level of depression (37.3%) prevailed, while there was no depression in the carriers of the C/C genotype of the IL-6 gene (24.2%; χ2 = 10.962; df=4; p=0.027). Carrying the C/G genotype of the IL-6 gene increased the chance of developing a severe level of depression by almost 2.9–3.3 times in comparison with the carriage of the C/C genotype. Among carriers of the G/G genotype of the IL-6 gene, a severe level of depression was 3.3 times more common than in carriers of the C/C genotype. Individuals carrying the G allele of the IL-6 gene were 1.6 times more likely to experience a severe level of depression than those carrying the C allele.Conclusion. The data obtained suggest that the carriage of the G allele of the G-174C polymorphism (rs1800795) of the IL-6 gene may be associated with a severe level of depression.

Introduction. The recurrence of diffuse large B-cell cell lymphoma in the central nervous system in the vast majority of cases is a fatal manifestation of the disease. The study of the lymphoma mutational profile can improve the accuracy of the prognosis of relapse in the central nervous system and justify the selection of patients for preventive treatment. Aim. To evaluate the mutational profile of cases of diffuse large B-cell cell lymphoma with central nervous system damage in relapse based on the results of our own experiment on high-performance sequencing.Materials and methods. On the Illumina platform, full-exome sequencing of diagnostic samples of diffuse large B-cell cell lymphoma with relapses in the central nervous system was performed. A panel including more than 70 genes was analyzed.Results. Four main groups of genetic events can be distinguished in the group of studied samples, namely: combined mutations in the NF-kB (MYD88, NOTCH1, CD79B, CARD11) and JAK-STAT (PIM1, STAT6) signaling pathways, as well as aberrations in the main oncosuppressor TP53 and chromatin remodeling system genes (ARID1A, KMT2D, EP300, SMARCA4). A recurrent mutation c. 794T>C, p.L265P MYD88 was detected in the study group. Among other findings, mutations in the CIITA and CD58 genes should be noted, which are important in avoiding tumor cells from immune surveillance.Conclusion. Despite the apparent heterogeneity of the mutational profile of diffuse large B-cell cell lymphoma with relapses in the central nervous system, in most cases, tumor cells were characterized by genetic disorders leading to the production of a large number of pro-inflammatory cytokines by malignant lymphocytes, as well as aberrations that reduce immunogenicity and contribute to the avoidance of immune surveillance by the tumor.

The aim of the study is to evaluate the association of some molecular genetic markers with progressive atherosclerosis.Material and methods. In total, the study included 202 patients (147 men and 55 women), who were divided into 2 groups. The 1st (main) group included patients with coronary artery disease (100 people) who had a combination of two or more cardiovascular events during the last 2 years before inclusion: myocardial infarction or unstable angina pectoris, arterial stenting for urgent indications (coronary and peripheral), stroke; acute ischemia, thrombosis or amputation of the lower extremities. The 2nd group (comparisons) included 102 patients with coronary artery disease who did not have any of the above cardiovascular events during the last 2 years before inclusion. DNA was isolated from peripheral blood samples by phenol-chloroform extraction.Results. In the group with progressive atherosclerosis at the age of 55 years and older, the AA rs3746444 genotype of the MIR499A gene was absent in both men and women, while in the control group its frequency reached 8.3 % (p = 0.044). The odds ratio of detecting the carriage of the heterozygous genotype AG of the rs6922269 polymorphism of the MTHFD1L gene in the group with progressive atherosclerosis is 0.5 times lower compared to the control group (95 % confidence interval 0.3–0.9; p = 0.034).Conclusions. Carrying the AA genotype rs3746444 of the MIR499A gene is a conditionally protective factor against the development of progressive atherosclerosis at the age of 55 years and older. Carrying the AG genotype of the rs6922269 polymorphism of the MTHFD1L gene is associated with a reduced likelihood of developing progressive atherosclerosis in patients with CAD.

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found.

The purpose of the study was to present up-to-date data on the frequency and significance of a number of p53-responsive oncosuppressive micrornas genes methylation in malignant neoplasms of the blood system.Material and methods. The search for available literary sources published in the Pubmed and RISC databases was carried out. A total of 399 articles were found, of which 62 were included in this review.Results. The p53 protein regulates a whole class of microRNAs – highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. МicroRNAs play an important role in all cellular processes and can have both oncosuppressive and pro-oncogenic properties. Impaired expression of p53-activated oncosuppressive micrornas in various tumors may be associated with specific epigenetic mechanisms (DNA methylation and histone deacetylation). The review examines the molecular and genetic characteristics of oncosuppressive micrornas functioning in normal hematopoiesis, the violation of expression of which is shown in the development of hemoblastoses, namely: miR-34a, miR-34b/c, miR-145, miR-143 and miR-203. It is known that the transcription of the genes of these microRNAs is carried out and regulated from their own promoters. The latest published research results on the diagnostic, prognostic and clinical significance of gene methylation of the microRNAs under consideration in malignant neoplasms of the blood system are presented. According to literature data, common targets for mir-34a, mir-34b/c, mir-145, mir-143 and miR-203 microRNAs are mRNAs of a number of pro-oncogenes, namely: transcription factor C-MYC, positive cell cycle regulators at the G1/S transition point of CDK4, CDK6 and CYCLIN-D1 phases, anti-apoptotic proteins MDM2, MDM4, BCL2 and MCL1, as well as DNMT3A and DNMT3B methyltransferases and other molecules. In this regard, it should be noted that there are positive feedbacks between p53 and microRNAs activated by it, as well as negative feedbacks between p53-responsive micrornas and C-MYC and DNA methyltransferases.Conclusion. Thus, the data presented in the review clarify the current understanding of the work of the regulatory network of the p53 protein and the micrornas activated by it, and also emphasize the functional association of p53-responsive microRNAs.

The study of sudden cardiac death (SCD) and its etiopathogenesis in cardiology practice remains one of the most pressing public health problems. In Western countries, SCD accounts for 20% of the total mortality and 50% of mortality associated with cardiovascular diseases. Considering the electrical instability in the myocardium as one of the main reasons for the development of life-threatening arrhythmias (ventricular tachycardia / ventricular fibrillation) and SCD, one should be aware of such provoking factors as ischemic heart disease, myocarditis, valvular heart disease, pharmacological influences, cardiomyopathy, and channelopathy. An increase or decrease in the duration of the QT interval, which reflects the work of ion channels, as well as ventricular depolarization and repolarization, increases the risk of SCD.The aim of this review was to study and analyze the available literature data on the relationship of molecular genetic markers with the duration of the QT interval.Currently, there is a number of genetic studies that allow to identify a large number of mutations and polymorphisms of known genes that affect the variability of the QT interval, showing their significance in risk stratification of sudden arrhythmic death and choosing the right tactics for managing, preventing, and treating patients, thus reducing the risk of SCD. The predictive value of genetic testing is the highest for long QT syndrome (LQTS), for which a gene-specific risk profile has been established, and lower for other channelopathies. A large amount of genetic data may be a promising approach to quantifying the risk of SCD, especially at a young age, which will be facilitated by further study of this problem.

Highlights. The association of single nucleotide polymorphic variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval was found in men of the Siberian population.Aim. To study the association of single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval.Methods. The study sample of men (1353 people) aged 25–69 years was formed from the DNA bank of participants in the international HAPIEE project and screening of young people 25–44 years old, residents of Novosibirsk. From each age subgroup (25–29, 30–34, …, 65–69 years old), about 10–15% of men with the shortest, average and longest QT interval were selected and the corresponding groups were formed. Genotyping of rs4657139 was carried out using PCR with RFLP (polymerase chain reaction followed by restriction fragment length polymorphism analysis). Genotyping rs12143842 – using RT-PCR (real-time polymerase chain reaction).Results. At the age of over 50 years, the CC genotype rs12143842 was detected in 66.1% of men in the group with a short and average QT interval and in 50.6% in the group with a long QT interval, while the TT genotype prevailed in the group with a long QT interval, 10, 8% of cases (odds ratio (OR) = 3.345, 95% confidence interval (CI) 1.149–9.739, p = 0.02). The homozygous TT genotype rs4657139 was more common in the long QT group, in 20.1% of cases, while the AA and AT genotypes predominated in the short, average QT groups (p = 0.041). A similar trend persists when separating by age in people over 50 years of age (p = 0.031) and when comparing genotype frequencies in the long and average QT groups in the model TT vs AA + AT & long QT vs short + average QT (p = 0.003).Conclusion. Single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene are associated with the duration of the QT interval in male residents of Novosibirsk.

Aim. To investigate polymorphisms of 18 genes as possible molecular genetic markers of predisposition or resistance to development of non-infective (NE) or infective endocarditis (IE).Materials and methods. The study encompassed 81 patients with NE and 94 patients with IE. The control group included 225 conditionally healthy people. Polymorphisms of 18 genes were tested using polymerase chain reaction (PCR).Results. For the first time, a statistically significant relationship was identified between gene polymorphisms and valvular vegetations: for genes in the hemostatic system – rs6025 (1691 G > A) of the F5 gene (AG genotype), rs1126643 (807 C > T) of the ITGA2 gene (TT genotype); for folate pathway genes – rs1805087 (2756 A > G) of the MTR gene (AG genotype) and rs11697325 (–8202 A/G) of the MMP9 gene (AA genotype) and rs2476601 (C1858T) of the PTPN22 gene (TT genotype). The protective effect of gene polymorphisms was revealed: for the NOS3 gene (4b / 4b genotype) and G (–572) C of the IL6 gene (CC genotype). For two polymorphisms, an association with thromboembolic complications in NE was revealed: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (–675 5G > 4G) of the PAI (SERPINE1) gene. In IE, such an association was detected for the polymorphism rs11697325 (–8202 A/G) of the MMP-9 gene.Conclusion. The polymorphisms of candidate genes were revealed, that are associated with the clinical and hemostasiological characteristics of IE and NE. In NE, for the first time, the association with thromboembolic complications was identified for two polymorphisms: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (– 675 5G > 4G) of the PAI-1 (SERPINE1) gene. In IE, such a relationship was detected for one polymorphism – rs11697325 (8202 A/G) of the MMP-9 gene.

The multifactorial genesis of hypertension (HTN) enforced the investigation of genetically determined component of its etiopathogenesis in various populations.The aim of present work is to assess the associations between blood pressure (BP) and HTN and polymorphism of a number of genetic markers identified according to GWAS data, in a case-control study based on Siberian population cohort. Design and methods. Design of the work—case-control study in the groups aged 45–69 years old based on a caucasoid population cohort (Novosibirsk). The group of cases included HTN subjects with established diagnosis of HTN under the age of 50 (n = 346)). The control included subjects matched by sex and age to cases, and having at least 2 examinations (6 months apart) with BP levels not exceeding “normal” BP by ESH, 2018 (n = 168). A total of 514 people were included in the analysis. We used standardized epidemiological methods to assess HTN and cardiovascular diseases. Single nucleotide polymorphisms (SNPs) were tested using real-time PCR (ABI 7900HT). The analysis included 16 markers identified in GWAS studies (rs11646213, rs17367504, rs11191548, rs12946454, rs16998073, rs1530440, rs653178, rs1378942, rs1004467, rs381815, rs2681492, rs2681472, rs3184504, rs2384550, rs6495122, rs6773957).Results. For the polymorphism rs1378942 of cytoplasmic tyrosine kinase gene (CSK), in a multivariable-adjusted logistic regression, the carriers of the AC/CC vs. AA genotypes had odds ratio (OR) of HTN of 1,51 (p = 0,043) independent of age and sex; this excess risk was partly explained by the impact of body mass index (BMI). With respect to the quantitative phenotype, women carrying the AA genotype had diastolic BP (DBP) value 5 mm Hg lower than carriers of AC/CC genotypes (p = 0,026). In a multivariable-adjusted analysis, the polymorphism rs653178 of ataxin 2 gene (ATXN2) was associated with HTN independent of age and BMI (СС vs ТТ/ТС; OR = 0,61; p = 0,022); this relationship was realized due to the contribution of men (p = 0,027). With respect to the quantitative phenotype, in the multivariable analysis, the carriers of СС genotype had DBP value lower than those with ТТ/ТС (p = 0,022) independent of age and BMI, and due to the contribution of men. In a multivariableadjusted analysis, the polymorphism rs6773957 of adiponectin gene (ADIPOQ) was associated with HTN in women regardless of age and BMI (GG v. AA/AG; OR = 0,29; p = 0,001). In unadjusted analysis, we found the association between polymorphism rs2384550 of T box transcription factor gene (TBX3) and the level of systolic BP (SBP) in men (p = 0,043); when comparing homozygous groups, the level of SBP was significantly higher among carriers of the AA genotype versus GG (p = 0,013), but this association was attenuated to insignificant in in a multivariate analysis.Conclusions. In a case-control study based on Siberian population sample, we found the associations between qualitative and quantitative phenotypes of BP/HTN and polymorphism of 4 SNPs (CSK, ATXN2, ADIPOQ, TBX3 genes). Our data replicated a number of positive results obtained in genomewide studies, and we obtained the evidence of new associations not previously convincingly shown, and of the context dependency of the association between HTN and a number of molecular markers.

The aim of the study was to evaluate the association of methylation of the F2RL3, CDKN2A gene with sudden cardiac death (SCD). Material and methods. Case-control study design. The SCD group included 150 deceased men (mean age 46.7 ± 9.2 years) with the main pathological diagnoses of acute circulatory failure, acute coronary insufficiency, which meets the SCD criteria of the European Society of Cardiology. The control group included 150 men who died suddenly, but not due to cardiovascular pathology (mean age 42.6 ± 1.2 years). DNA was isolated by phenol-chloroform extraction from myocardial tissue in both groups. The methylation status of the F2RL3 gene (19: 16890405-16890606, GRCh38.p13) and the CDKN2A gene (9: 21974726-21974877, GRCh38.p13) was assessed by methyl-specific polymerase chain reaction. Results. In the SCD group, 17.3 % (26/150) had the F2RL3 gene completely methylated (MM); in 6.0 % (9/150) it is completely unmethylated (UU); 76.7 % (115/150) had both methylated and unmethylated F2RL3 (MU) gene. In the control group, 16 % (24/150) had the F2RL3 gene completely methylated (MM); in 5.3 % (8/150), it is completely unmethylated (UU); 78.7 % (118/150) had both methylated and unmethylated F2RL3 (MU) gene. When comparing the groups, there were no statistically significant differences in the methylation status of the F2RL3 gene between the groups (p > 0.05). In all subjects in the SCD group and the control group, the CDKN2A gene is completely unmethylated. Conclusions. Methylation of genes F2RL3, CDKN2A is not associated with sudden cardiac death.

The objective of the study: to study rs2227983 polymorphism of EGFR gene in patients with allergic asthma and healthy individuals.Subjects and Methods. 179 patients suffering from allergic asthma were included in the study. The diagnosis and degree of severity were established in accordance with the GINA recommendations. The Control Group included apparently healthy individuals (n = 217). Patients with allergic asthma underwent standard laboratory and instrumental examinations and DNA typing.Results. A statistically significant predominance of AG genotype frequency in the group of patients with allergic asthma, including women, versus the group of healthy individuals, was established. AG rs2227983 genotype of EGFR gene was found to be significantly more common in patients with mild and moderate allergic asthma including women, than in healthy individuals, including women.Conclusion. The association of rs2227983 polymorphism of EGFR gene with allergic asthma has been established. A homozygous GG genotype may play a protective role against the disease.

BACKGROUND: «The vicious circle» of associations of diabetes mellitus (DM) with pancreatic pathology, when pancreatic diseases can initiate DM, and type 2 DM — cause functional and organic pancreatic pathology, determines the search for possible associations. Some studies have established a relationship between TNF or TP53 polymorphisms with DM or with pancreatic diseases.AIMS: to determine and compare fasting plasma glucose and the frequency of hyperglycemia in patients with acute pancreatitis (APp), chronic pancreatitis (CPp), pancreatic cancer (PCp) depending on gender, etiology or stage of the disease, polymorphism -308G/A TNF gene in all patients, and polymorphism 72Arg/Pro gene TP53 in PCp..MATERIALS AND METHODS: At the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: frequency of hyperglycemia in APp, CPp, PCp, considering the polymorphism TNF and TP53 genes. RESULTS: The lowest age-standardized fasting plasma glucose (FPG) was found in CPp (6,2±0,2 mmol/l) than in APp (6,7±0,2 mmol/l, p=0,041). In PCp (6,6±0,2 mmol/l), the average levels of FPG did not differ substantially when compared with APp (p=0,749) or CPp (p=0,092). In APp, the norm of GP was detected less frequently (31,8%) than in CPp (54,6%, χ2 =6,3, p=0,012), and the frequency of the norm of GP in PCp (48,9%) did not differ with that in APp or CPp. The frequency of FPG≥6,10,05. In PCp genotypes Arg/Arg, Arg/Pro, Pro/Pro polymorphism gene 72Arg/Pro TP53 in 2,4, 35,7, 61,9% of cases. No associations of GP≥7,0 mmol/l with TNF polymorphism in APp, CPp, PCp and with TP53 polymorphism in PCp were obtained.CONCLUSIONS: The frequency of FGP≥7,0 mmol/l did not differ for various pancreatic disease and was not associated with the risk of pancreatic necrosis and “defined” CP. The -308G/A polymorphism TNF gene did not differ in APp, CPp or PCp and was not associated with impaired carbohydrate metabolism. The 72Arg/Pro polymorphism TP53 gene in PCp was not associated with impaired carbohydrate metabolism.

Introduction. The article discusses the problem of using cognitive visceral cardiobiofeedback as a preventive and non-drug method for correcting disturbed regulation mechanisms associated with an increase in blood pressure in adolescents with essential hypertension (EH) against the background of standard antihypertensive therapy with enalapril. Aim of the study was to investigate the indices of the cardiointervalogram (CIG) during a biofeedback session and to evaluate the effectiveness of cardiobiofeedback in healthy adolescents and adolescents with EH living in Novosibirsk.Material and methods. Each participant underwent a 5-minute CIG recording using the hardware and software complex VedaPulse under physiological rest and during biofeedback session. In the course of biofeedback, the subject was asked to lengthen the expiration phase of the respiratory cycle with parallel relaxation of muscle tone and visual feedback on the dynamics of a multimedia plot reflecting changes in the duration of the cardiac cycle.Results and discussion. We found that the effectiveness of cardiorespiratory synchronization (CRS) is characterized by an increase in SDNN indicators by 8.3% and the total power of spectral influences (TP) by 23.6% due to a significant increase in the parasympathetic spectral index of HF by 29.4%. An increase in the power index of the spectrum of low-frequency oscillations (LF) by 51.3% can be considered as an element of CRS within 0,1 Hz. In healthy adolescents, the reactivity of the suprasegmental levels of regulation (IC) is preserved and their growth is noted by 7.6%. In adolescents with EH, an increase in the duration of the cardiac cycle by 5.2% and TP by 31.2% was recorded in the course of cardiobiofeedback, which is associated with an increase in the power of the spectrum of high-frequency oscillations (HF) by 2.4%. This phenomenon should be considered as a positive pathophysiological response of the autonomic link of the nervous system, which is recorded by a decrease in blood pressure.Conclusion. We assume that the test with cognitive visceral cardiobiofeedback can serve as an effective marker for the analysis of the rigidity of autonomic mechanisms of regulation in adolescents with essential hypertension. Conscious regulation of the heart rate through the mechanism of controlled respiration (biofeedback) can be an effective non-drug method for correcting autonomic regulation disorders in adolescents with arterial hypertension, which is manifested by a significant decrease in blood pressure.

Aim . A study of the association of the methylation of the promoter of the ABCA1 gene with sudden cardiac death (SCD). Materials and methods . The study design is based on the case-control principle. The SCD group included 150 men (mean age (46.7 ± 9.2) years) who died of sudden cardiac death according to forensic medical examination data (the main pathological diagnoses are acute circulatory failure, acute coronary insufficiency). The control group included 150 men (mean age (42.6 ± 1.2) years) who died suddenly, but not due to cardiovascular pathology. DNA was isolated by phenol-chloroform extraction from myocardial tissue. The methylation status of the ABCA1 gene promoter was assessed by methyl-specific polymerase chain reaction. The results obtained were statistically processed in SPSS 16.0 using Pearson’s test and Fisher’s test with Yates’ correction for continuity. P < 0.05 was used as a level of significance. Results . Comparing the groups revealed statistically significant differences in the methylation status of the gene promoter ( p = 0.015). In the SCD group, the proportion of individuals whose ABCA1 gene promoter is methylated is statistically significantly higher compared to the control group ( p = 0.020; OR = 5.86; 95% CI (1.28–26.89)). Conclusion. Methylation of the promoter of the ABCA1 gene is associated with sudden cardiac death.

Aim.To study the association of single-nucleotide polymorphismrs3025058(5а/6а) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors for its development. Materials and methods.The study involved 260 patients with stroke (age [57.0; 51.062.0]) and 272 patients of the control group (age [55.0; 51.062.0]). Among the patients who underwent stroke, 157 men and 103 women. The control group included 170 men and 102 women. The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of the extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. The patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of extracranial brachiocephalic arteries, disorders of the hemostasis system. The control group was examined within the framework of the international project HAPIEE. Molecular genetic research was carried out by real-time PCR. Statistical processing of the material was carried out using the Statistica for Windows 7.0, Excel and SPSS 22 application software. Results.The study established statistically significant associations between the 5a/5a genotype and the 5a allele and stroke in the general group of patients, as well as in the subgroup of men, subgroups of patients with extracranial brachiocephalic arteries atherosclerosis and dyslipidemia. In the subgroup of patients with cardiac arrhythmias, statistically significant results were obtained only for allele 5a, and in the subgroup of women with stroke, subgroups of patients with arterial hypertension and hypercoagulation, no significant associations ofrs3025058(5a/6a) polymorphism with stroke were found. Conclusion.Genotype 5a/5a and allele 5a of the single-nucleotide polymorphismrs3025058(5а/6а) increase the risk of stroke in individuals from the East Siberian population, including those in the presence of such risk factors as extracranial brachiocephalic arteries atherosclerosis and dyslipidemia.

The article presents a literature review on the study of the relationship of FGA, FGB, F2, F5, PAI, ITGA2 gene polymorphisms with the development of pulmonary embolism (PE). We concluded that genetic factors in the development of PE are to a greater extent mutations in the F2, F5, PAI, ITGA2 genes. There is a positive correlation between the presence of combined genetic mutations and the development of PE. The study of allelic polymorphism of hemostasis genes makes it possible to predict coagulation system disorders, including PE.

Cerebrovascular accident (CVA) in patients with various cardiovascular diseases is a life-threatening complication, the development of which can be contributed by both environmental and genetic factors, the understanding of which is necessary to determine the tactics of treatment and predict the disease course. The article presents a brief review of studies on genetic predictors of CVA, in particular the association of the ABCA1 rs2230806 polymorphism and the risk of CVA in cardiovascular patients. Targeted studies of associations of the ABCA1 rs2230806 polymorphism with cerebrovascular diseases in the Russian Federation, except for studies at our university, could not be found.

In this literature review, we analyzed studies on the influence of genetic specifics of patients on the restoration of myocardial contractility after acute myocardial infarction. Data on the influence of genetic characteristics on the myocardial repair, remodeling process, and the restoration of cardiac contractility are presented. The use of genetic methods in the examination of patients and further consideration of individual characteristics when prescribing therapy will make it possible to implement a personalized approach to each patient. This will improve the effectiveness of treatment and the disease prognosis.

Aim. To study associations of rs2464196 and rs11212617 polymorphisms with the development of myocardial infarction (MI) in combination with type 2 diabetes (T2D).Material and methods. The study included two groups: main group (n=115) — patients with prior myocardial infarction and T2D, comparison group (n=116) — patients with myocardial infarction without T2D, hospitalized from December 1, 2018 to December 31, 2019 at the Regional Vascular Center № 1 of the City Clinical Hospital № 1. Participants were comparable in sex and age. Patients underwent clinical and instrumental investigations, a genetic test for single nucleotide polymorphisms, which showed associations with the development of MI and T2D according to genome-wide association study (GWAS): rs2464196 of the HNF1A gene, rs11212617 of the ATM gene.Results. Carriage of the AA genotype of the HNF1A rs2464196 polymorphism was found to be associated MI in combination with T2D in the general group (odds ratio (OR), 3,180, 95% confidence interval (CI), 1,206-8,387, p=0,015). After division of the group by sex, significant differences remained only in women (OR=9,706, 95% CI, 1,188-79,325, p=0,011).Conclusion. The data obtained can make it possible to identify a priority group of patients for personalized prevention of cardiovascular diseases.

Aim . To study the association of new polymorphisms with sudden cardiac death (SCD) in men. Material and methods . The SCD group (n=278) was formed using guidelines of the World Health Organization and the European Society of Cardiology. The autopsy material was taken from the men who died suddenly outside the prevention and treatment facilities who underwent medicolegal examination according to a standard protocol. The average age in the SCD group was 53,2±8,7 years. The control group (n=274) was selected by sex and age from the DNA bank formed during the international studies of MONICA and HAPIEE. The mean age of men in the control group was 53.±8,3 years. Genomic DNA was separated from myocardial tissue and venous blood by the method of phenol-chloroform extraction. Rs10503929, rs7121, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms were tested using real-time PCR. The insertion- deletion polymorphisms rs.0692285 and rs39.7 were genotyped by PCR with flanking primers followed by polyacrylamide gel electrophoresis. Statistical analysis was performed using the SPSS 13.0 software package. Results . By comparison the frequencies of rs7121 genotypes in the studied groups of Novosibirsk, an increase in the proportion of CC genotype carriers in the group with SCD (OR=.6, 95% CI 1,1-2,2; p=0,025) was found. The carriage of the rs.0692285 ID genotype reduces the risk of SCD (OR=0,6, 95% CI 0,4-0,9; p=0,0M). A carriage of the rs39.7 ID genotype increases the risk of SCD (OR=.5, 95% CI 1,1-2,2; p=0,020). Conclusion . The rs7121 of the GNAS gene, the rs.0692285 of the RYR2 gene, and the rs39.7 of the COL1A2 gene are associated with SCD. Rs10503929, rs6730157, rs11720524, rs7737692, rs7521023 polymorphisms do not associate with SCD in the men of Novosibirsk.

Aim . To confirm association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs6582147 rs 10010305, rs2136810, rs17797829, identified as the most likely candidate markers. Material and methods . The SCD group (n=360, mean age 53,0±9,2 years, men — 76,9%, women — 23,1%) was formed using the SCD criteria of the European Society of Cardiology. The control group (n=402, mean age 52,9±9,1 years, men — 69,7%, women — 30,3%) was selected by gender and age from the DNA bank of international studies MONICA, HAPIEE. DNA is separated by phenol-chloroform extraction. Genotyping was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results . The GT rs6582147 genotype is associated with a protective effect on SCD (OR=0,671, 95% CI 0,496-0,909, p=0,011), and the GG genotype with an increased risk of SCD (OR=1,598, 95% CI 1,195-2,135, p=0,002). The greatest effect was in the group of men over 50 years old (p

Genetic background of hypertension (AT) and blood pressure (BP) regulation is extensively investigated in genome-wide association studies (GWAS). The findings from recent GWAS require replication in independent samples. Aim . To investigate the association between BP and AT in Russian population and several single nucleotide polymorphisms identified in GWAS. Material and methods . In the frame of “case-control” design we recruited subjects with AT diagnosed at age below 50 according to the criteria of BP >140/90 mm Hg and/or receiving antihypertensive therapy, and subjects with normotension according to 2 examinations from population sampling, Novosibirsk, totally included 514, men/women aged 45-69 years). From published GWAS we selected 24 genetic markers related to hypertension, 8 markers were included for present analysis (rs 13082711, rs1173771, rs13107325, rs3918226, rs1799945, rs805303, rs1458038, rs932764). Standard epidemiological methods were used (BP measurement, anthropometry, medical history of AT and treatment, risk factors of AT, socio-demographic parameters). Single nucleotide polymorphisms (SNPs) were tested using real time PCR. Results . In studied sample we replicated the association between rs3918226 (promoter region of gene of endothelial NO synthase; eNOS) and systolic BP (T-allele carriers had 9 mm Hg higher systolic BP than CC carriers in men, p=0,049 independent of age). New association was found between rs 932764 (gene of phospholipase-c-epsilon-1 isoform, PLCE1) and AT (heterozygotes genotype AG was protective in men, p=0,017 independent of age and body mass). The association between rs13107325 (gene of soluble carrier family 39/zinc transporter/member 8, SLC39A8) and systolic BP was confirmed (in men, С-allele carriers had higher systolic BP values then TT carriers, p=0,044, multivariable adjusted). Conclusion . In analysis of relationship between phenotypes of BP and AT and 8 genetic markers of AT in Russian population sample we replicated two known associations, revealed new association and identified new data on modulating effect of sex and body mass. These replications in newly studied Siberian population, different from early studied populations by risk factors profile, climate, geographic and other parameters, support the involvement of identified or close loci in potential mechanisms of AT susceptibility.

Aim . To study association between polymorphisms of candidate genes and the development of non-infectious and infectious endocarditis (IE). Material and methods . During the study 175 patients were examined. They were divided into two groups: the first group — 81 patients with non-infectious endocarditis and the second one — 94 patients with IE. We present a comparative analysis of the genotype frequencies of the five genes polymorphisms: rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, rs4340 of the ACE gene, rs2476601 (С1858Т) of the PTPN22 gene, rs231775 (49 A/G) of the CTLA4 gene in groups of patients with endocarditis and healthy individuals. Results . We found association between endocarditis and rs11697325 (-8202 A/G) of the MMP9 gene, 4a/4b of the NOS3 gene, as well as rs2476601 (C1858T) of the PTPN22 gene with IE. Conclusion . Thus, association between three of the five polymorphisms and vegetations on the valvular heart apparatus was revealed.

In this paper, we propose a structure of a uniaxial wheeled module (UWM) with an instrument platform having two degrees of freedom with respect to the wheelset axle, which moves without slippage over an underlying surface. The horizontal orientation of the platform from its small neighborhood is done by precessional motion with the one-axis powered gyroscopes installed on the platform. The horizontal stabilization of the platform is done by the reactive moments of flywheel motors and the gravitational moments of weights whose displacement is controlled by the function of the flywheels’ rotational speeds. The data on the horizontal deviations of the platform are provided by accelerometric sensors, which are not exposed to inertial forces. A mathematical model of the UWM is developed and control structures for its flywheels, weights, and gyroscopes are synthesized. The effectiveness of the structures proposed is confirmed by the numerical simulation of the UWM’s trajectory tracking behavior over the underlying surface.

Aim. To evaluate the utilization of complex significance evaluation in Russian population, of genetic markers of myocardial infarction identified in entire-genomic associative studies. Material and methods . Group of MI patients (n=200) and control group (n=420) were created based on populational selection of 45-69 year old citizens of Novosibirsk (9400 persons), collected during the international project HAPIEE; myocardial infarction patients, admitted to intensive care unit of the Hospital № 1 (160 persons); sudden cardiac death victims, post forensic investigation (n=285). Longevity group was collected during home visits and in the nursing houses (n=85). Genomic DNA was extracted from venous blood and myocardial tissue by phenolchlorophorm method. Genes polymorphism was tested with PCR real-time according to the protocol by equipment developer (TaqMan, Applied Biosystems, USA), device ABI 7900HT. For the study, the following MNP were selected: rs499818, rs619203, rs10757278 and rs1333049 (chr. 9), rs1376251, rs2549513, rs4804611, rs17465637. Results. Mononucleotide polymorphisms, that did not show differences at pretest stage, showed significant distinctions in the studied population. Two MNP were closely linked: rs10757278 and rs1333049 (chr. 9) so for further assessment the rs1333049 was retained. Among other seven, only five MNP showed relation with MI of various strength. Some, like the rs1333049 showed association with MI in all groups and subgroups, while the others — only in separate groups, with restriction by sex and gender. The rs2549513 and rs17465637 showed to be not associated with CHD at all, though rs2549513 showed association with lipid and glucose metabolism, as with the severity of coronary atherosclerosis and adverse prognosis for 1 year post-MI. The rs17465637 was just poorly associated with BMI. Conclusion. Complex approach to assessment of polymorphism role is quite demanding, but provides with a high grade of insurance in the significance of the results obtained, of non-random character of the results, and makes it to choose the most credible, that have showed association not only with the main pathological phenotype, but with its risk factors.

A method for controlling the angular orientation with respect to the horizon plane of the platform of a uniaxial wheeled module moving without slippage over the underlying surface is considered. For a module involving a one-axis gyroscope, a compensating flywheel, and a stabilizing weight, equations of motion are derived, which describe the module as a nonholonomic system due to the absence of slippage of its wheels over the underlying surface. The conditions for the "force of undisturbability" of the platform by the inertial forces upon its arbitrary translational-rotational motion and the conditions for "informational undisturbability" by the inertial forces of the accelometric sensor of the deviation of the platform from the horizon plane are determined. The analytical relationships determining the conditions for the absence of slippage of the wheels are found. By numerical simulation, rational values of the coefficient in the laws governing the moments of forces developed by the control elements of the structure are obtained. The effectiveness of these laws is confirmed by the results of simulating the control processes over the angular motion of the platform of the module along a typical trajectory of its motion over the underlying surface.

The paper considers a design of integrated navigation system of a single-axis wheeled module used to perform various functions in airdrome infrastructure. The core of the integrated navigation system is a strapdown inertial navigation system integrated with a video camera and dynamic model of a single-axis wheeled module with nonholonomic contact with underlying surface. The integrated navigation system simultaneously estimates the module navigation parameters and the coordinates of the landmarks observed by the video camera. The system is shown to determine the navigation parameters and to construct the structural map of landmarks over rather long periods without external aiding.

Based on studies of certain gene-candidate polymorphism, the authors studied markers of early development and unfavorable course of pneumoconiosis in post-contact period. Analysis covered occurrence of genotypes and allels of I/D polymorphism of gene CCRS, 4a/b polymorphism of gene NOS3, VNTR polymorphism of gene ILRN, I/D polymorphism of CASP8 and mutation GLU342LYS (rs28929474) and GLU264VAL (rsl7S80) in gene SERPINAl in patients with various terms of pneumoconiosis formation. Findings are individual criteria of early formation and progress of pneumoconiosis in post-contact period..

to establish associations of candidate genes ACE, AGT, AGTR1, ADRB1, ADRA2B, MTHFR and NOS3 polymorphisms with left ventricular myocardial hypertrophy (LVH) in patients with arterial hypertension (AH) among the indigenous (the Shors) and non-indigenous population of Mountain Shoria.We examined 788 people in a clinical and epidemiological study of compactly living population in the remote areas of Mountain Shoria, located in the south of Western Siberia (468 members of indigenous ethnic group [the Shors], 320 members of non-indigenous ethnic group [90% Caucasian]). Diagnosis of AH was set in accordance with recommendations of Society of Cardiology of the Russian Federation/Medical Society of the Russian Federation on the Problem of Arterial Hypertension (RMOAG) (2010). Assessment of the structural and functional state of myocardium in patients with AH (n=201 among Shors and 158 among non-indigenous residents) was made by echocardiography. The polymorphisms of genes ACE (I/D, rs 4340), АGT (c.803TC, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145AG, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677СТ, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested by PCR.Among patients with AH LVH occurred more often within the indigenous (Shor) than in non-indigenous (non-Shor) ethnic group (51.5 vs 42.2%, respectively, p=0.034). The frequency of homozygous genotype I/I of the ACE gene among AH patients with LVH in the Shor group was higher than in the non-Shor group (41.2 vs 19.3%, p=0.004). The prevalence of mutant genotype A/A of the ADRB1 gene was lower in the Shor compared to non-Shor group (53.6 vs 75.0%, p=0.014). The percentage of the carriers of prognostically favorable genotype 4b/4b of the NOS3 gene was higher in Shor than in non-Shor group (71.9 vs 52.7%, p=0.018), while the percentage of homozygous genotype 4a/4a carriers in the Shor group was lower (2.1% vs 18.2%, p=0.008).The following studied genes were found to be associated of with LVH: in the Shor cohort - the MTHFR gene (log additive model of inheritance), the A/G genotype of the ADRB1 gene (among people with normal body weight), the I/D genotype of the ACE gene (among men); in the non-indigenous cohort - D/D genotype of the ACE gene (the codominant model of inheritance), the NOS3 gene (the log additive model of inheritance).

Aim. To study the association of polymorphisms rs1800795 of gene IL-6 with the development of sick sinus node syndrome (SSS). Material and methods. Totally, 109 patients studied, with idiopathic SSS, and 59 of their healthy relatives of I, II, III grade of relation, and 173 controls. Patients from main group were selected to subgroups according to sex and clinical type of the disease. All patients underwent standard clinical and instrumental cardiological assessment and molecular-genetic test of DNA. Statistics was done with software “Statistica 7.0”. Results. There was significant predominance of homozygous genotype of rare allele of the studied gene in controls (18,5%±3,0) comparing to idiopathic SSS patients (8,5%±3,1), p=0,039, and to subgroup of males with SSS (5,2%±8 among SSS males versus 30,8%±9,1 among controls, р=0,03). Also there was significant predominance of the widespread genotype IL-6 among males with compensated SSS variant (69,2%±12,8) comparing to the controls (23,1%±8,3, р=0,005). Conclusion. Probably the homozygous genotype GG of gene IL-6 is protective against idiopathic SSS.

We develop a control system of a nonholonomic measuring uniaxial wheeled module designed for monitoring the geometrical parameters of airfield pavements. Using a nonlinear approach, we synthesize a trajectory control subsystem based on a kinematic model of a nonholonomic unicycle locomotion control subsystem using the partial feedback linearization approach. We present the results of the numerical simulation of the synthesized control system with disturbances.

Adverse cardiovascular manifestations (ACVM) were registered during 7-year follow-up of young patients with undifferentiated connective tissue dysplasia (CTD). ACVM developed in 28.42% of patients. Most frequent ACVMs were extension/aneurysm of the thoracic aorta (10.75%), cerebral vascular syndrome (10.56%), and arrhythmias (9.11%). Most significant risk factors for extension/aneurysm of the aorta were pathology of vertebral arteries, common risk factors (arterial hypertension, alcohol/drugs, smoking, heavy physical work, sports activities), bicuspid aortic valve); for pathology of cerebral vessels -completely open Willis Circle, pathology of vertebral arteries, CTD related changes of skin and spine, diagnostic CTD coefficient23, chronic diseases of veins; clinically significant cardiac rhythm disturbances - combined valve manifestations of CTD, myxomatous degeneration of heart valves, pathology of the aorta, male sex, metabolic changes of the myocardium, deviations of circadian index, predominance of sympathetic tone, and diastolic dysfunction. Analysis of clinical characteristics (age, symptoms and severity of CTD, QTc dispersion more or equal 50 ms) and presence of unfavorable genetic polymorphisms in 1-adrenergic receptor gene (Ser49Gly, rs1801252), transcription factor Sp4 gene (A80807T, rs1011168), genes of matrix metalloproteinases type 3 (5A/6A) and type 9 (8202 A/G) allowed to evaluate overall risk of ACVM.

The main principles of the environmental standardization of hazardous impacts experienced by natural ecosystems and approaches to this standardization based on the analysis of in situ biological and physicochemical monitoring are described. The possibilities of applying standardization methods are discussed, including methods based on background and averaged values of the characteristics to be standardized, a model analysis of the effect of abiotic components on natural communities, and in situ technology of establishing local environmental standards. Some principles underlying the environmental standardization are presented. The classification of ecosystems by their environmental quality is described.

The basic systematic approaches to ecological standardization of pollutants in natural environment were described with regard to the nature conservation legislation of Russia and other countries. Some special features and shortcomings of the standards of maximum admissible concentrations (MAC) for pollutants were analyzed in comparison to the standards of admissible impacts used in Russia. The efficiency of applying standard integral indices using the values obtained in the laboratory and based on MAC was studied for their application to assessing water quality.

The identification of human predisposition genes to severe forms of infectious diseases is important for understanding the mechanisms of pathogenesis, as well as for the detection of the risk groups. This will allow one to carry out targeted vaccination and preventive therapy. The most common approaches to the genetic risk estimation include conducting association studies, in which the groups of patients and control individuals are compared using both preliminarily selected candidate genes and using genome-wide analysis. To search for genetic variants predisposed to severe forms of infectious diseases, it is expedient to form a control that consists of patients with clinically proven infections with asymptomatic or mild forms of the disease. The examples of the use of these approaches to identify genetic factors that predispose one to severe forms of infections caused by viruses from the Flaviviridae family are considered in the review. At present, a number of genetic markers associated with predisposition to tick-borne encephalitis, West Nile fever, and Dengue fever have already been detected. These associations must be confirmed in independent samples. Genetic variants, for which the association with spontaneous recovery during infection with hepatitis C virus, patient's reaction on antiviral drugs, and the development of liver fibrosis was established, were also detected. The gene variants with more pronounced phenotypic effects will probably be found during further studies; they can be used in clinical practice as prognostic markers of the course and outcomes of infection with the Flaviviridae, as well as of the response to treatment.

The relationship between β(2)-adrenoreceptor gene Arg16Gly polymorphism and bronchial cold reactivity has been studied. Genotype Arg16Arg and allele Arg16 carriership is associated with the development of cold bronchospasm in asthmatics. In addition, a significant reduction of 3,5'-cyclic adenosine monophosphate (cAMP) level has been recorded in Arg16Arg homozygotes on minute 30 after cold provocation in comparison with Gly16Gly genotype carriers. These data indicate the influence of primary dysfunction of β(2)-adrenoreceptors for the formation of bronchial cold hyperreactivity in the patients. Reduced cAMP synthesis by cells in Arg16Arg carriers indicates congenital liability of their β(2)-adrenoreceptors to desensitization during cold air isocapnic hyperventilation test.

Examples are given of the application of bioestimation—a conceptually new hydrobiological method used to control the process of water quality formation. This paper is the continuation of the paper “Bioestimation: A New Method for the Control of Water Self-Purification Process and Its Comparison with Bioindication”. The experience in the use of bioestimation in water bodies with different use type, size, salinity, flowage, and geographic position confirmed its universal character, information value, promptness, and the possibility to limit the volume of sample to be sent to 10–20 cm3, thus simplifying the field works. Each significant factor, which affects the self-purification process, is identified independently, since the bioestimators reflecting it are biotically independent; their number varies depending only on changes in the environmental factors that are external with respect to the community of environmental factors. Bioestimation shows prognostic properties, since it makes it possible to prevent water quality deterioration and to restore the normal course of water self-purification at the stage of its quality formation. The use of bioestimation will extend the positive anthropogenic impact on water bodies.

The feasibility of ecological standardization of physicochemical factors that do not refer to concentrations of polluting substances (water regime, water temperature, and pH) is confirmed. The opportunity of standardization is provided with the approach developed by the authors, which is based on joint analysis of the data of biological and physicochemical monitoring. Additional opportunities provided by the method used for the analysis are connected with calculating the admissible influence values that vary in time. The seasonal dynamics of the obtained ecologically tolerable levels (ETL) for factors disturbing the well being of biological indicators is investigated. The water sample points are analyzed concerning their ecological well being or ill being depending on observance or nonobservance of ETL values.

A literary review devoted to the methods of ecological forecast is presented. A classification of forecasts is made according to the degree of system homogeneity (point or distributed), the period of forecast (short-term, medium-term, and long-term), and the level of detail. Qualitative and quantitative methods of forecast are distinguished. The qualitative methods include morphological analysis, the method of expert evaluation, and the analog method. The quantitative methods imply modeling intended for quantitative forecast (estimation) of indicative biological characteristics using imitation and regression methods.

The dataset on benthic fauna diversity obtained by ecological monitoring of lakes (Mari El Republic) was analyzed for applicability in water quality biological benchmark. The effect of several parameters on biodiversity were tested: (1) calculation errors in species number definition, (2) application of certain evaluation method of rank distribution parameters, (3) adequacy degree of distribution model, (4) evenness: diversity ratio, (5) hydrochemical parameters of lake, and (6) “sampling site effect” (natural reserve area impact). The biodiversity characteristics were suggested, which highly correlated to obtained data. The critical level for each characteristic was proposed to define favorable and adverse conditions of benthic communities. Practical recommendations were given for using studied parameters in the evaluation of the water quality biological benchmark in Mari El Republic.