Gene of the month:<i>TMPRSS2</i>(transmembrane serine protease 2)

Thunders, Michelle; Delahunt, Brett

doi:10.1136/jclinpath-2020-206987

Cited by 88 publications

(104 citation statements)

References 36 publications

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“…The human TMPRSS2 gene is located in chromosome 21.q22.3. It encodes protein that contains a transmembrane domain, low-density lipoprotein receptor class A (LDLRA) domain, scavenger receptor cysteine-rich (SRCR) domain and serine protease catalytic domain [16]. At least six nucleotide variants within the human TMPRSS2 coding region that cause amino acid substitutions have been identi ed.…”

Section: Tmprss2 Polymorphism and Patient's Outcomementioning

confidence: 99%

Initial Study on TMPRSS2 p.Val160Met Genetic Variant in COVID-19 patients

Wulandari¹,

Hamidah²,

Pakpahan³

et al. 2021

Preprint

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BackgroundCoronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load.ResultsWe genotyped 95 patients with COVID-19 hospitalized in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant with the severity of the disease. However, we identified significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. ConclusionOur data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of Covid-19.

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Section: Tmprss2 Polymorphism and Patient's Outcomementioning

confidence: 99%

Initial Study on TMPRSS2 p.Val160Met Genetic Variant in COVID-19 patients

Wulandari¹,

Hamidah²,

Pakpahan³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…SARS-CoV-2 enters human ACE2-expressing cells mainly via endocytosis, in which cathepsin L and other components are critical [ 26 ]. TMPRSS2 primes the viral spike protein in order to facilitate ACE2-mediated viral entry and extra-pulmonary spread [ 27 ]. Besides TMPRSS2, HSPGs are cell surface receptors that assist ACE2 in endocytosis-mediated coronavirus entry [ 28 ].…”

Section: Pathogenesis Of Covid-19mentioning

confidence: 99%

Cardiovascular protective properties of oxytocin against COVID-19

Wang

2021

Life Sciences

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“…ACE2 is a cellular receptor for the viral entry of SARS-COV-2. Viral S protein utilizes ACE2 receptor to fuse into the host cell membrane or enter via endocytosis and this process is regulated by type II transmembrane serine proteases (TTSPs) such as the TMPRSS2 [ 99 ]. Lung is one of the major organs with elevated ACE2 levels and ACE2 expression is significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), compared to normal tissues [ 100 , 101 ].…”

Section: Lung Cancer and Covid-19: The Molecular Linkmentioning

confidence: 99%

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Ahmad

Manzoor

Siddiqui

et al. 2022

Seminars in Cancer Biology

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Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

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Gene of the month:TMPRSS2(transmembrane serine protease 2)

Cited by 88 publications

References 36 publications

Initial Study on TMPRSS2 p.Val160Met Genetic Variant in COVID-19 patients

Initial Study on TMPRSS2 p.Val160Met Genetic Variant in COVID-19 patients

Cardiovascular protective properties of oxytocin against COVID-19

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

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