Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
| Autor: | Sergey Litvinov, Irina Khitrinskaya, Elza Khusnutdinova, Vadim Stepanov, V. N. Kharkov, N. A. Kolesnikov, Aitalina Sukhomyasova, A.V. Markov, M. G. Swarovskaya, N. R. Maksimova, Natalia Ekomasova, Murat Dzhaubermezov, A. V. Marusin, Magomed Radjabov, Aleksei A. Zarubin, O. V. Shtygasheva |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
ACE2 BSG urologic and male genital diseases Exon 0302 clinical medicine Gene Frequency Protein Interaction Mapping Missense mutation Copy-number variation Molecular Targeted Therapy Genetics (clinical) Genetics Serine Endopeptidases Exons Europe 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Receptors Virus Angiotensin-Converting Enzyme 2 Single-Cell Analysis pharmacotranscriptomics Asia Curcumin lcsh:QH426-470 TMPRSS2 Gene Mutation Missense Single-nucleotide polymorphism Biology TMPRSS2 Gene Expression Regulation Enzymologic Article 03 medical and health sciences microRNA expression SNV Humans Genetic Predisposition to Disease Gene Acetaminophen SARS-CoV-2 Genetic Variation COVID-19 Pharmacogenomic Testing COVID-19 Drug Treatment MicroRNAs lcsh:Genetics 030104 developmental biology Pharmacogenomics Basigin |
| Zdroj: | Genes, Vol 12, Iss 19, p 19 (2021) Genes Volume 12 Issue 1 |
| ISSN: | 2073-4425 |
| Popis: | 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&ndash gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|