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Статья
Structural variability, expression profile, and pharmacogenetic properties of tmprss2 gene as a potential target for covid-19 therapy
2021
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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Версии
- 1. Version of Record от 2021-04-27
Метаданные
Название журнала
- Genes
Том
- 12
Выпуск
- 1
Страницы
- 1-16
Ключевые слова
- ACE2 protein, human; BSG protein, human; CD147 antigen; coronavirus spike glycoprotein; curcumin; microRNA; paracetamol; serine proteinase; spike protein, SARS-CoV-2; TMPRSS2 protein, human; virus receptor; Asia; biosynthesis; drug effect; drug therapy; epidemiology; ethnology; Europe; exon; gene expression regulation; gene frequency; genetic predisposition; genetic variation; genetics; human; metabolism; missense mutation; molecularly targeted therapy; pharmacogenetic testing; physiology; protein analysis; single cell analysis; therapy; Acetaminophen; Angiotensin-Converting Enzyme 2; Asia; Basigin; COVID-19; Curcumin; Europe; Exons; Gene Expression Regulation, Enzymologic; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Humans; MicroRNAs; Molecular Targeted Therapy; Mutation, Missense; Pharmacogenomic Testing; Protein Interaction Mapping; Receptors, Virus; SARS-CoV-2; Serine Endopeptidases; Single-Cell Analysis; Spike Glycoprotein, Coronavirus
Издатель
- MDPI AG
Тип документа
- journal article
Тип лицензии Creative Commons
- CC
Правовой статус документа
- Свободная лицензия
Источник
- scopus
