The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene–gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.

To determine mtDNA haplogroups in the populations of Balkars ( N = 235) and Karachays ( N= 123), the nucleotide sequence of the hypervariable segment 1 (HVS1) and polymorphism of 20 markers...

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.

Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, endogenous hormones, and drugs, including those used in COVID-19 treatment. Cytochrome p450 genes are linked to the pathogenesis of some multifactorial traits and diseases, such as cancer, particularly prostate cancer, colorectal cancer, breast cancer, and cervical cancer. Genotyping was performed on 540 supposedly healthy individuals of 5 Finno-Permic populations from the territories of the European part of the Russian Federation. There was a statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; data on the rs3892097 locus of the CYP2D6 gene shows that Izhemsky Komis are different from the Mordovian and Udmurt populations.

BACKGRAUND: Cytochrome P450 is an enzyme involved in the metabolism of phase I xenobiotics, toxins, endogenous hormones and pharmaceuticals. AIM: Is studying the polymorphism of the CYP1A1 gene (Ile462Val, rs1048943) in the Turkic-speaking populations of the central part of the North Caucasus Region (Balkars and Karachays). MATERIALS AND METHODS: We analyzed DNA isolated from leukocytes of peripheral venous blood of a total of 177 unrelated Balkars and Karachays (104 Balkars, 73 Karachays). RESULTS: The ethnicity of the studied individuals was established, indicating their ancestors up to the third generation. The method of genotyping was performed by real-time PCR using competing TaqMan probes. As a result: the frequency of the 462Val variant in the sample of Balkars was 8,6% (95% CI 5,2113,33), slightly above the frequency range found in European populations. In the sample of Karachays, the frequency of the 462Val allele was 7,5% (95% CI 9,8213.08), which is the upper limit of values typical for European populations. CONCLUSION: In the Turkic-speaking populations of the central part of the North Caucasus, the CYP1A1 462Val allele occurs with a frequency characteristic of the Near Eastern and European 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.