Miscarriage is a multifactorial disease, the development of which is caused by the interaction of many factors, including genetic ones, among which special attention is paid to polymorphic variants of sex hormone receptor genes (ESR1, PGR). The data of a number of scientific papers on the association of single nucleotide polymorphisms rs9340799 and rs2234693 of the ESR1 gene and rs10895068 of the PGR gene with the risk of miscarriage in women are ambiguous, which is probably due to population characteristics of the frequency distribution alleles and genotypes of the indicated SNPs. The data of our study are aimed at studying the role of rs9340799 and rs2234693 of the ESR1 gene and rs10895068 of the PGR gene in the development of miscarriage in women living in the city of Chelyabinsk and the Chelyabinsk region. The material for the study was DNA samples isolated from peripheral venous blood leukocytes. The analysis of single nucleotide gene polymorphisms was carried out by real-time PCR. It was found that the C allele and the C/C genotype rs2234693 of the ESR1 gene is significantly more often registered in the group of women with a history of up to 2 abortions, as well as in the group of apparently healthy women without a burdened obstetric and gynecological history. Based on the data obtained, it can be assumed that the C allele and the C/C genotype rs2234693 of the ESR1 gene have a probable protective effect on the risk of recurrent miscarriage.

Schizotypy is considered as a phenotype that reflects preclinical manifestations of a genetic predisposition to schizophrenia. There are two views on the nature of this relationship - dimensional and taxonomic. Previous studies on the contribution of schizophrenia polygenic risk scores (PRS) to schizotypy were conducted in Western European populations using the dimensional model and yielded negative results. The objective of this study was to assess the relationship between schizophrenia PRS and dimensions and taxa of schizotypy in the Russian population. Methods. Genome-wide data were obtained from a sample of 290 healthy subjects belonging to the clusters of individuals with low, positive, negative, and high mixed schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ). Results. The schizophrenia PRS did not correlate with cognitive-perceptual, paranoid, interpersonal, or disorganized SPQ factors. Taxon-like groups (clusters) differed in PRS at a trend level, with the highest PRS being found in the high mixed schizotypy group. Conclusion. The results are consistent with the assumption of the taxonomic model of schizotypy that in some healthy individuals with a high degree of schizotypal personality traits, these traits reflect the genetic predisposition to schizophrenia.

Immune checkpoint inhibitors (ICIs) have made a revolutionary breakthrough in the cancer treatment, particularly clear cell renal cell carcinoma (ccRCC), but a substantial proportion of patients show therapy resistance. The reasons for the different treatment outcomes are still unclear. MicroRNAs involved in the regulation of many cancer and immune cell pathways are actively studied as potential biomarkers. Some microRNAs are factors determining the ICI efficacy. We analyzed the associations of rs57095329 and rs2910164 polymorphic variants of microRNA-146a with the risk of complications and resistance during ICI treatment in 86 patients with metastatic ccRCC. Association analysis of rs2910164 showed that CC genotype and the C allele had a higher risk of developing severe immune-mediated reactions when treated with ICIs.

Decidualization defects in early gestation are known to lead to fetal growth retardation, miscarriage, or various obstetric complications. The aim is to reveal the transcriptomic profile of decidual cells (DC) in severe preeclampsia in Russians and Buryats. A full-transcriptomic analysis of placenta DC was carried out in representatives of two ethnic groups (Russians (n=4) and Buryats (n=4)). Single DC were obtained using laser microdissection technology and thin stained section preparations. When comparing expression profiles of DC in the examined groups, statistically significant differences (FDR<0.05) were revealed for 61 transcripts. Most of the identified differentially expressed genes (DEGs) were characterized by overexpression in Russian samples, while only 15 genes showed a high level of expression in Buryats. The results obtained indicate that the pathways of the innate immunity system associated with the activity of interferon proteins predominate in the differentiation of the DC transcriptomic profile of Russian and Buryat women with preeclampsia, which was confirmed not only by functional annotation of the list of identified DEG genes, but also by network analysis of data.

Chronic viral hepatitis C (HCVC) is a multifactorial disease with a complex genetic component. The present study examined the involvement of the PMS2 gene in the development of HCVC and the progression of fibrosis to cirrhosis. The frequencies of alleles and genotypes of rs1805321 in the PMS2 gene were analyzed in patients with chronic hepatitis C (n=150) and in a population samples from the Tomsk (n=345). The association of the studied marker with HCVC was established: the C allele (p=0.00005) and the CC genotype (p=0.013) predispose to the development of pathology, the TT genotype is protective (p=0.00002). Allele C has been shown to predispose to the development of liver cirrhosis (p = 0.038). The studied SNP may also affect the rate of progression of liver fibrosis in HCVC.

An analysis of intergenic interactions in relation to the risk of developing schizophrenia (in the population of Russians and Kazakhs) and Alzheimer’s disease (in the population of Russians) was carried out using the Multifactor Dimensionality Reduction (MDR) method. 16 combinations of genotypes associated with a high or low risk of developing schizophrenia or Alzheimer’s disease were identified: 7 combinations of genotypes of the VRK2, ZNF804A, ZFP67P genes for schizophrenia in the Russian population, 7 combinations of genotypes of the KCNB2, ZFP64P, NRIP1 genes for schizophrenia in the Kazakh population, two combinations of genotypes APOE and CSMD1 genes for Alzheimer’s disease in the Russian population. The results of the work indicate that the cumulative contribution of risk gene variants plays an important role in the development of pathology in diseases with cognitive impairment.

The genetic relationship of 22 multifactorial and 6 Mendelian diseases based on data extracted from the curated DisGenNet database were studied. The coefficient of genetic «commonality» between diseases was calculated and as well as methods of clustering and prioritization were used. As a result, a pronounced common hereditary component of multifactorial diseases of various pathogenetic groups was established. The assessment of molecular similarity between Mendelian and multifactorial diseases is significantly limits due to incomplete knowledge about the contribution of genes.

Among oncological pathologies lung cancer is the most crucial problem. For revealing of molecular and genetical structure of lung cancer it was conducted transcriptome analysis using material of peripheral blood mononuclears of lung cancer patients and healthy individuals. One-color microarray analysis was used as an essential experimental method. Functional enrichment analysis of gene groups using sources of biological databases (Gene Ontology, KEGG и Reactome) allowed to conduct annotation of obtained results. It was obtained data about differentially expressed gene groups, involved in specific biological signaling pathways. Among them gene clusters of immune response, protein synthesis and cell cycle had maximum level of functional enrichment. Gene cluster of specific and innate immune response components (FCGR2A, FCGR2C, FCGR2B, C5AR, IL6R, CXCL8), and also factors of tuberculosis resistance (ATP6V0B, MAPK14, ITGAX, CORO1A) had decreased level of expression. Decreased expression was also detected for genes, involved in protein synthesis (EIF4A2, EIF4A1, RPL23). For genes of T-cellular signaling pathway (RASGRP1, PDCD1, CD3G, PIK3R1, CD8A) and also for apoptosis factors (PDCD1, CCR7, CCR5, IL1A) was determined enhanced level of their synthesis. Conclusion. Genes that were detected as result of conducted analysis can be used as diagnostic markers of lung cancer development.

Alternative splicing (AS) of mRNA is a key stage of post-transcriptional regulation of gene expression, which ensures the expression of various isoforms of RNA. Probably, this mechanism plays an important role in the development and functioning of the placenta. Decidual cells (DC) were chosen as the object of research due to their key role in physiological pregnancy. Whole transcriptome sequencing of DC RNA of placental tissue samples obtained from patients with the physiological pregnancy was performed, during which 151233 AS events in 352 genes were identified. It is noteworthy that two or more AS events characterized only 130 genes. These genes are involved in the canonical Wnt signaling pathway, regulation of substrate-dependent cell migration, activation of androgen receptors, and mRNA splicing. The maximum number of alternative events per gene established for the FN1 gene, the product of which is associated with the development of preeclampsia and is a screening marker of premature birth. The study suggests the prospects for further exploring of the distribution of alternatively spliced isoforms of the FN1 gene in a cohort of patients with both physiological pregnancy and obstetric pathology.

The present study aimed to assess the effect of DNA methylation and genetic variants of the hypothalamic-pituitary-adrenal system with phenotypic variance in depression in 1065 mentally healthy individuals controlling for sex and ethnicity. As a result of linear regression analysis, the association of polymorphic loci rs53576, rs7632287 and rs2254298 of the OXTR gene, rs1042615 and rs3803107 of the AVPR1A gene, as well as rs28632197 of the AVPR1B gene with depression level was revealed. In addition, the association of the methylation status of the OXT (Р=0,003; OR=2,12) and AVPR1A (Р=0,013; OR=3,38) genes and an increased risk of developing depression was found. The results contribute to understanding the biological basis of depression and identifying biomarkers of depressive behavior.

Atherosclerosis is a multicomponent disease that depends on immune response, and physiological condition of the arteries. Innate and adaptive immunity act as a driver of the pathogenesis of atherosclerosis rather than play an atheroprotective role. T-lymphocytes, as a key part of the immune response, can exhibit both pro- and anti-atherogenic properties. In this regard, the study of this cell population is of particular interest. In the present study, we performed the analysis of T-cells subpopulations depending on the T-cells to macrophages ratio. We applied bioinformatics methods to three single-cell RNA-sequencing datasets of human coronary and carotid arteries downloaded from the SRA database (SRP199578, SRP274629, SRP287809). The present study demonstrated a direct proportionality between CD8+ T memory stem cells (TSCM) and the ratio of the CD8+ T cells pool to the macrophage pool. In addition, we revealed differences in TSCM receptors (IL2RA, SELP, LEPR, SDC2, CCR6, TGFBR3, IL1R2, CD247, CXCR6, LIFR, ERBB3) that are involved in ligand-receptor interactions with other atherosclerotic plaques cell populations, between two groups of patients with high and low CD8+ T-cells to macrophages ratio.

The aim of our study was to assess the involvement of polymorphic variants of genes responsible for the regulation of glutamatergic and GABAergic neurotransmission in the formation of differences in the volume of working memory in 1011 university students of the Republic of Bashkortostan and the Republic of Udmurtia. As a result of linear regression analysis, the association of the polymorphic locus rs4971648 of the NRXN1 gene was shown (p = 0.008; β = - 0.84) with variations in the amount of working memory in smoking individuals.The obtained data contribute to the understanding of the molecular genetic mechanisms underlying individual differences in the amount of working memory.

Schizophrenia is a multifactorial disease resulting from genetic disorders and unfavorable conditions of embryonic development and later life. The study revealed a pronounced negative correlation between markers of DNA damage in blood lymphocytes (oxidation marker 8-oxodG, double-strand break marker γH2AX) and the repeat content - satellite III subfraction (located in pericentromeric heterochromatin 1q12) in a sample of patients with schizophrenia in the acute stage (N = 97). The low content of the f-SatIII repeat in the DNA of leukocytes of patients can be considered as a potential marker of the level of both chronic oxidative stress and DNA damage in schizophrenia.

Aim. Study the association of FTO rs9939609, TCF7L2 rs7903146, rs1799883 FABP2 polymorphisms on the risk of morbid obesity in women. Materials and methods. The morbid obesity group (n=192, average age 57.02 ± 7.16 years, BMI > 40 kg/m2) and the control group (n=450, average age 55.44 ± 7.41 years, BMI 20-25 kg/m2) were formed from the DNA bank of the international HAPIEE research. Genotyping was performed by PCR-RFLP and real time PCR using TaqMan (Applied Biosystems, USA). The results were statistically processed in the SPSS software. Results. There were no statistically significant differences in the genotype frequencies of TCF7L2 rs7903146, FABP2 rs1799883 (р>0.05) between the morbid obesity group and the control group. The morbid obesity group has the number of TT genotype carriers of FTO rs9939609 polymorphism less (26,6%) and AT genotype more (53,6%) than in the control group (38,4%; 45,1%, respectively), (OR=0.58, 95%CI 0.4-0.84, p=0.004; OR=1.41, 95%CI 1.003-1.98, p=0.047, respectively). Conclusion. AT genotype of FTO rs9939609 is the genotype of the risk of morbid obesity in women and TT genotype has a protective effect against it. Polymorphisms TCF7L2 rs7903146, FABP2 rs1799883 were not associated with morbid obesity in the studied group of women.

Published data indicate a decreased relative leukocyte telomere length (RLTL) in individuals diagnosed with clinical alcohol dependence; at the same time, to date no association of clinical and anamnestic characteristics with telomere shortening in patients with alcohol addiction were reported. The present study aimed to assess the association between RLTL and the risk of developing chronic alcoholism, and to identify individual differences in RLTL in addicted patients accounting for clinical and anamnestic parameters. As a result of the analysis, no statistically significant differences in RLTL were demonstrated between patients and control group (β=-0.044, p=0.437). However, we observed more rapid telomeres shortening with age in patients with alcoholism (β=-0.246, p=0.007) compared with healthy donors (β=-0.151, p=0.050). A statistically significant effect of the inclusion in the regression model of such clinical and anamnestic characteristics as the age of onset of withdrawal syndrome (β=-0.385, p=0.001) and alcohol abuse (β=-0.254, p=0.006) on telomere shortening was identified. The data obtained confirm the acceleration of cellular aging of the organism based on RLTL in individuals who alcohol addiction.

The aim of this study was the identification of SNPs in 3’-UTR microRNA (miRNA) target sequences, underlining individual drug susceptibility, based on available data on eQTL and allele-specific expression (ASE) analysis. Methods and Algorithms: The search for SNPs in 3’-UTR miRNA target sites was carried out in 253 ASE events identified upon exposure of 5 human cell types to various drugs, nutrients and pollutants [1] and in 5402 eQTLs that appeared upon treatment of CD14+ monocytes with IFN-γ [2]. Data on the functional impact of SNPs on predicted miRNA sites were taken from the PolymiRTS database. Results: Of the 5402 eQTLs identified under IFN-γ treatment, 317 contained predicted miRNA binding sites affected by the nucleotide substitution. The highest enrichment in the group of 317 eQTLs was shown for the terms «cellular response to stress» (41 genes) and «immune response» (36 genes). Out of 253 ASE events, 58 coincided with the predicted SNPs in 3’-UTR miRNA target sequences. In most cases, reduced expression of the allelic variant corresponded to the appearance of a binding site for a particular miR(s). Conclusion: Both eQTL and ASE analysis are effective tools to identify SNPs located in 3’-UTR miRNA target sequences and associated with individual drug response.

Among malignant neoplasms of the organs of the female reproductive system, ovarian cancer (OC) leads in the number of deaths. The molecular mechanism of ovarian tumor development contains a variety of genetic and epigenetic events that cause activation of oncogenes and inactivation of tumor suppressor genes underlying malignant cell transformation [2]. The TP53 gene is one of the tumor suppressor genes. Violation or insufficient functioning of the protein product of this gene leads to the development of various oncological diseases, including ovarian cancer. This paper presents an associative analysis of the variant rs17878362 of the TP53 gene with the risk of ovarian cancer in women from the Republic of Bashkortostan.