Murat A. Dzhaubermezov

Today, infectious diseases occupy a leading position among other diseases causing concerns among the population, leading to a decrease in work capacity and a number of serious complications. Monitoring infectious diseases and preparing for future outbreaks is crucial for the development of genetic epidemiology and public health in general. In this study, we analyzed the allele and genotype frequency distribution of the rs10774671 (G>A) variant of the OAS1 gene, previously associated with infectious diseases, in subpopulations of Bashkirs and Tatars living in the Volga-Ural region. We paid special attention to the study of subpopulations to obtain the most accurate results of the frequency distribution of this locus in such large populations as Bashkirs and Tatars. A study of the allele and genotype distribution of the rs10774671 genetic variant of the OAS1 gene was conducted using PCR followed by RFLP analysis. A pairwise comparison of allele frequencies between the studied populations revealed statistically significant differences between the Permsky Bashkirs subpopulation and the Askinsky, Burzyansky and Orenburgsky Bashkirs subpopulations (p<0.05). The Ewens-Watterson test for the total Bashkirs sample, including all the studied subpopulations, demonstrated the presence of balancing selection (Fo=0.5405, Fe=0.6461, p<0.05). A separate analysis of each subpopulation revealed the effect of balancing selection on the Orenburgsky Bashkirs (Fo=0.4375, Fe=0.5957, p<0.05). These results will add to our knowledge of the distribution of the rs10774671 genetic variant of the OAS1 gene in populations worldwide.

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.

Background: Thiopurines, including azathioprine and 6-mercaptopurine, are widely used in the treatment of inflammatory and autoimmune diseases, as well as hematological malignancies; however, their use is limited by the risk of severe myelosuppression. Pharmacogenetic variants in the TPMT and NUDT15 genes significantly affect drug tolerability, and their frequencies vary markedly across ethnic groups, making population-based studies of these markers in different regions of Russia particularly important. Aim: To assess interethnic variability in the frequencies of clinically relevant TPMT rs1142345 and NUDT15 rs116855232 polymorphisms in populations of the Volga-Ural region, North Caucasus, and the Lower Volga region. Methods: Data from 1687 healthy males from 27 populations and 15 ethnogeographic groups (Bashkirs, Tatars, Mordvins, Chuvash, Mari, Udmurts, Komi, Besermyans, Kalmyks, Balkars, Karachays, Circassians, Ingush, Chechens, and Moldovans), collected during field expeditions in 2000–2025, were retrospectively analyzed. Information on date and place of birth, family history of disease, ethnicity of parents and grandparents (maternal and paternal lines), and causes of death of closed relatives was collected by questionnaire. Individuals with mixed ancestry were excluded. Genomic DNA was extracted from venous blood; genotyping of TPMT rs1142345 and NUDT15 rs116855232 was performed by real-time polymerase chain reaction with TaqMan probes. Results: The minor allele rs1142345*C of TPMT (TPMT*3C) was rare or absent in most of the studied groups, with the highest frequencies observed in Chuvash (3.65%), Circassians (3.23%), and Mordvins (3.16%). The minor allele rs116855232*T of NUDT15 (NUDT15*3) was more frequent in Kalmyks (15.6%), Bashkirs from Perm Krai (14.77%), and Bashkirs of the Samara and Saratov Regions (14.63%), whereas it was absent in Moldovans and occurred at minimal frequencies in Mordvins (0.52%), Chechens (1.03%) and Ingush (1.61%). The most significant differences in NUDT15*3 allele frequency were observed between Kalmyks and Mordvins (15.60% vs 0.52%; p = 2.7 × 10-9, p_FDR = 9.3 × 10-7), Kalmyks and Chechens (15.60% vs 1.03%; p = 2.4 × 10-8, p_FDR = 3.8 × 10-6), and Kalmyks and Moldovans (15.60% vs 0.0%; p = 3.2 × 10-8, p_FDR = 3.8 × 10-6). Among the Bashkir subgroups, the greatest differences were found between Bashkirs from Perm Krai and Mordvins (14.77% vs 0.52%; p = 1.4 × 10-6, p_FDR = 1.3 × 10-4), between Bashkirs from Samara and Saratov Regions and Mordvins (14.63% vs 0.52%; p = 2.5 × 10-6, p_FDR = 1.8 × 10-4), and between Bashkirs from Perm Krai and Moldovans (14.77% vs 0.0%; p = 3.4 × 10-6, p_FDR = 2.0 × 10-4) and Chechens (14.77% vs 1.03%; p = 8.0 × 10-6, p_FDR = 3.5 × 10-4). Conclusion: The results confirm substantial ethnic heterogeneity in the distribution of pharmacogenetic markers of thiopurine toxicity. The minor allele rs116855232*T of NUDT15 was significantly more prevalent in the studied populations than the minor allele rs1142345*C of TPMT, and its frequencies in several groups were comparable to those in East Asian populations. This supports the utility of genotyping for personalizing azathioprine therapy in Russian regions.

Prostate cancer (PrC) is one of the most common malignancies among men worldwide. However, the contribution of genetic variation in microRNA (miRNA) biogenesis pathway genes to PrC susceptibility remains poorly characterized in many ethnically diverse populations. We conducted a case–control study involving 532 PrC patients and 550 controls from the Volga-Ural region of Eurasia to evaluate the association of twenty-one single nucleotide polymorphisms (SNPs) with PrC risk using single-variant and polygenic approaches. Association analyses identified rs595055 in the AGO1 gene as significantly associated with PrC risk after correction for multiple testing. To evaluate the cumulative effect of genetic variation, weighted and unweighted polygenic risk scores (PRSs) were constructed. The weighted PRS was significantly associated with PrC risk (odds ratio per standard deviation increase = 1.63, 95% CI [1.43–1.85], P = 1.37 × 10⁻¹³), and demonstrated moderate discriminatory performance (AUC = 63.1%), outperforming the unweighted model. Individuals in the highest PRS quartile had approximately threefold higher odds of PrC than those in the lowest quartile. Combining the weighted PRS with prostate-specific antigen improved discrimination (AUC = 68.1%). These findings support the contribution of miRNA biogenesis pathway genes to PrC susceptibility and highlight the potential value of pathway-based polygenic risk stratification in understudied populations.

Cytochrome P450 is an enzyme involved in the phase 1 metabolism of xenobiotics, toxins, endogenous hormones, and drugs. This study examines the population genetic aspects of the distribution of the polymorphic variant rs1065852 of the CYP2D6 gene in Finno-Ugric populations. The study of the CYP2D6 gene in Finno-Ugric populations of Russia is of paramount importance for Russian pharmacogenetics, as the genetic heterogeneity of these groups leads to significant differences in the frequencies of pharmacogenetic markers. This necessitates a differentiated approach to personalized therapy and precludes the extrapolation of averaged European data to the indigenous peoples of the Russian Federation. The study involved 329 presumably healthy individuals from five Finno-Ugric populations across the Russian Federation. Genotyping of the polymorphic variant was performed using TaqMan real-time PCR technology. The studied populations demonstrate significant variability and form a clear intraregional gradient, and overall, they are close to other European groups but differ statistically significantly from East Asian populations.

Introduction. High-altitude conditions are a factor of natural selection that affects the physiological and genetic mechanisms of human adaptation to hypoxia. One of the genes involved in the regulation of the cellular response to oxygen deficiency is HIF1A. The rs11549465 polymorphic variant of this gene results in a Pro582Ser substitution and is characterized by functional differences, which makes it of interest for study in population and adaptive contexts. Goals. The study aims to investigate the distribution of alleles and genotypes of the rs11549465 polymorphic variant of the HIF1A gene in Balkar and Karachay populations, and to assess its possible association with adaptation to high-altitude hypoxia. Materials and methods. DNA isolated from peripheral blood samples of representatives of two populations of the North Caucasus has been used as research material: Balkars (N=100) and Karachays (N=99). A comparative analysis of the frequencies of alleles and genotypes of rs11549465 performed between the studied populations. Results. The C allele predominated in both studied populations, while the frequency of the T allele varied between the samples. Statistically significant differences were identified between the Balkar and Karachay populations. The distribution of the T allele did not demonstrate a direct dependence on the historical association of the populations with high-altitude territories. Conclusions. The results obtained indicate interpopulation differentiation of rs11549465 among the studied peoples of the North Caucasus. The identified differences do not allow a causal relationship between rs11549465 and adaptation to high-altitude conditions to be established; however, the functional significance of this variant indicates the potential for further investigation of its possible role in adaptation to hypoxia.

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.

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.