Genes (Basel) . Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy

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Genes (Basel)


. 2020 Dec 25;12(1):E19.
doi: 10.3390/genes12010019.
Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy


Aleksei Zarubin ¹ , Vadim Stepanov ¹ , Anton Markov ¹ , Nikita Kolesnikov ¹ , Andrey Marusin ¹ , Irina Khitrinskaya ¹ , Maria Swarovskaya ¹ , Sergey Litvinov ² , Natalia Ekomasova ² , Murat Dzhaubermezov ² , Nadezhda Maksimova ³ , Aitalina Sukhomyasova ³ , Olga Shtygasheva ⁴ , Elza Khusnutdinova ² , Magomed Radzhabov ⁵ , Vladimir Kharkov ¹



Affiliations

• PMID: 33375616
• DOI: 10.3390/genes12010019

Abstract

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.

Keywords: ACE2; BSG; COVID-19; SARS-CoV-2; SNV; TMPRSS2; expression; pharmacotranscriptomics.