Yuliya Fedorova

Gastrointestinal diseases, including gastric cancer (GC), peptic ulcer disease (PUD), and chronic gastritis (CG), remain a serious public health concern worldwide and are characterized by a multifactorial etiology. This study aims to evaluate the contribution of the rs4988235 polymorphism of the MCM6 gene, which determines lactase persistence, to modulating the risk of these pathologies. Genotyping was performed on 1304 DNA samples (205 patients with CG, 336 with PUD, 340 with GC, and 423 healthy controls). Statistical analysis revealed that the frequency of the T allele was highest in Russians (35.8%) and lowest in Bashkirs (22.3%). No associations with the risk of GC or PUD were found (p>0.05). In Tatars, the CT genotype was identified as a marker of reduced risk for CG (OR=0.49; p=0.03). Thus, significant interethnic differences were observed in the distribution of rs4988235 genotype frequencies of the MCM6 gene; however, the differences in the distribution of the studied parameters between patients and controls did not reach a level that would support the prognostic significance of this locus for assessing the risk of CG, PUD, or GC.

Ovarian cancer remains one of the most common causes of death from gynecological cancer in women worldwide. Its course depends on many factors, including genetic and epigenetic disorders. MicroRNAs are currently considered one of the most promising prognostic and diagnostic markers for solid tumors. The aim of the study was to analyze the association of polymorphic loci of the microRNA-27a rs895819 and microRNA-146a rs2910164 genes with the risk of developing ovarian cancer.Material and Methods. Genotyping was performed by determining single nucleotide polymorphisms using the KASP method. For pairwise comparison of the frequency of occurrence of genotypes and alleles in patients with ovarian cancer and in the control group, the χ2 test was used for 2×2 contingency tables. If there are statistically significant differences between the compared samples, the odds ratio (OR) and the boundaries of the 95 % confidence interval (95 % CI) were assessed. Quantitative characteristics were compared using the Mann – Whitney test (in the case of two groups) and the Kruskal – Wallis test (in the case of three groups).Results. As a result of a comparative analysis of the distribution of frequencies of alleles and genotypes of the polymorphic locus rs2910164 of the miR-146a gene in a sample of patients with ovarian cancer and healthy individuals, it was shown that carriage of the homozygous genotype GG and allele G is a risk factor for women of Tatar ethnicity. No significant differences were detected in the distribution of allele frequencies and genotypes of the rs895819 polymorphic locus of the miR-27a gene.Conclusions. The polymorphic locus of microRNA-146a rs2910164 is associated with an increased risk of ovarian cancer in women of Tatar ethnicity.

Background and objective — Gastric cancer (GC) is one of the most common cancers worldwide with a high mortality rate. Hereditary predisposition to GC is still not fully understood. The objective of this study was to compare the prevalence of mutations in the BRCA1 (c.68_69delAG, c.4035delA, c.5266dupC, c.3700_3704delGTAAA, c.3756_3759delGTCT, c.181T>G, c.1961delA), BRCA2 (c.5946delT), CHEK2 (c.1100delC, c.115+1G>A) and NBS1 (c.657_661delGTTTT) genes in patients with GC and healthy donors from the Volga-Ural region of Russia. Methods — The material for the study was DNA samples from 415 patients with GC and 400 healthy donors. Genomic DNA was isolated from peripheral blood lymphocytes using sequential phenol-chloroform extraction. Genotyping of mutations was performed using real-time polymerase chain reaction with DNA melt curve detection. Results — A total of 8 individuals with a heterozygous germline mutation were identified: 2 patients with GC of Bashkir and Tatar nationality had c.5266dupC in the BRCA1 gene, 1 Tatar woman with GC had c.3756_3759delGTCT in the BRCA1 gene, 2 men with GC of Russian nationality were carriers of c.657_661delGTTTT in the NBS1 gene, 2 patients with GC of Tatar and Russian nationality were carriers of c.115+1G>A in the CHEK2 gene, and 1 Tatar woman from the control group had c.181T>G in the BRCA1 gene. Conclusion — These results open up new opportunities for studying the molecular basis of GC and developing targeted treatments for patients with these mutations. Further research is needed to fully uncover the clinical potential of these findings and improve the treatment of GC in affected populations.

Background. The major candidate genes for ovarian cancer (BRCA1/2) explain no more than 15–20 % of cases; therefore it is important to focus on the search for new molecular genetic markers. The aim of the study was to analyze the association of rs11549465/HIF1A, rs3025039/VEGFA, and rs2146323/VEGFA polymorphic variants with the risk of developing ovarian cancer in women from the Republic of Bashkortostan. Material and methods. Our research included DNA samples of women with ovarian cancer (n=205) and women without cancer at the time of blood sampling (n=259) from the Republic of Bashkortostan. Genotyping was carried out using the Real Time PCR method based on TaqMan technology. Results. Polymorphic variants, such as rs11549465/HIF1A, rs3025039/VEGFA, and rs2146323/VEGFA were not associated with the risk of developing ovarian cancer in women of the Republic of Bashkortostan. However, the rs11549465/HIF1A polymorphic locus was significantly correlated with the grade of tumor cell differentiation, and the rs3025039/VEGFA was associated with lymph node metastasis. Conclusion. These polymorphic variants may be associated with ovarian cancer prognosis. to confirm this association, it is necessary to conduct research on a large sample size.

In recent years, statistical studies show that cholelithiasis is detected in every fifth woman and every tenth man. Сholelithiasis is a multifactorial process that is influenced by both environmental and genetic factors. Some evidence suggests that total plasma homocysteine correlates with the presence of gallstones, suggesting that hyperhomocysteinemia is a risk factor for cholelithiasis. The aim of this work was to analyze the association of polymorphic variants of the methylenetetrahydrofolate reductase MTHFR (rs1801133 (677C>T), rs1801131 (1298A>C)) and methionine synthase reductase MTRR (rs1801394 (66A>G)) genes with the development of gallstone disease in individuals from the Republic of Bashkortostan. Material and methods. DNA samples from 196 patients with cholelithiasis and DNA samples from 274 individuals in the control group aged 23-87 years living in the Republic of Bashkortostan were used as research material. Genotyping was performed using the real-time PCR method. Results. It has been established that the rs1801133*T allele and the rs1801133*TT genotype of the MTHFR gene are markers of an increased risk of developing cholelithiasis. An association was established between the rs1801133*TT genotype of the rs1801133 polymorphic variant of the MTHFR gene and the moderate severity of cholelithiasis and hereditary burden in patients with cholelithiasis. A study of the polymorphic variant of the MTRR gene revealed that the rs1801394*G allele increases the risk of developing cholelithiasis. Analysis of associations of the polymorphic variant rs1801131 of the MTHFR gene with the development of cholelithiasis did not reveal statistically significant differences between the compared groups of patients and controls. Conclusion. Determination of homocysteine levels and genetic testing of polymorphic variants of MTHFR and MTRR in patients with cholelithiasis may be useful in clinical practice.

The work examines the main mechanisms responsible for the process of acclimatization of the population of high mountain regions to the conditions of hypobaric hypoxia. The purpose of this review is to describe the pathways of genetic, epigenetic and physiological control in the adaptation of indigenous populations of highlands to reduced barometric pressure and oxygen tension in the environment. It has been shown that populations living in different high-mountain regions demonstrate different ways of adaptation in response to a decrease in the partial pressure of oxygen in the inspired air. The changes that occur in the body in response to stressful conditions are extremely diverse. These include changes in the respiratory, cardiovascular, hematological systems and cellular adaptation. In this review, we examine genomic variations leading to evolutionary adaptation to life at high altitudes, gene expression, pathophysiological and metabolic features, and long-term adaptation in various high-altitude populations. We also consider the peoples of the Caucasus as one of the most promising populations for further study of complex adaptation mechanisms.

Background — According to epidemiological studies, nearly 7 million people in Russia suffer from bronchial asthma (BA), of which 1 million have a severe form of the disease that is difficult to control. Insufficiently effective control of BA leads to a reduction in the quality of life, the development of its more severe forms, an increase in the frequency of exacerbations of the disease, and an increase in the number of disability and death cases in patients. Objective — The goal of our research was conducting a long-term cohort study of BA in adults living in the Republic of Bashkortostan and assessing the clinical and prognostic value of internal and external risk factors for exacerbation and death from BA. Methods and Results — We analyzed the medical records of 213 BA patients 18 to 67 years а age from 2012 through 2022. Genotyping of six SNPs in ADRB2 (rs1042713, rs1042714), CRHR1 (rs242939, rs1876828), NR3C1 (rs41423247), and HRH3 (rs3787429) genes was performed by real-time polymerase chain reaction. Using regression analysis, we assessed predictors of the risks of exacerbation and death in BA and built multivariate models for each outcome. Conclusion — As a result of regression analysis, significant clinical and prognostic risk factors for re-exacerbation and death from BA were identified.

Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. Hereditary predisposition for GC is not fully elucidated so far. The aim of this study was identification of possible new candidate genes, associated with the increased risk of gastric cancer development. Whole exome sequencing (WES) was performed on 18 DNA samples from adenocarcinoma specimens and non-tumor-bearing healthy stomach tissue from the same patient. Three pathogenic variants were identified: c.1320+1G>A in the CDH1 gene and c.27_28insCCCAGCCCCAGCTACCA (p.Ala9fs) of the VEGFA gene were found only in the tumor tissue, whereas c.G1874C (p.Cys625Ser) in the FANCA gene was found in both the tumor and normal tissue. These changes were found only in patients with diffuse gastric cancer and were absent in the DNA of healthy donors.