Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human

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dc.contributor.authorSenapati, S
dc.contributor.authorKumar, S
dc.contributor.authorSingh, A.K
dc.contributor.authorBanerjee, P
dc.contributor.authorBhagavatula, S.
dc.date.accessioned2020-07-16T07:41:52Z
dc.date.accessioned2024-08-13T10:34:50Z
dc.date.available2020-07-16T07:41:52Z
dc.date.available2024-08-13T10:34:50Z
dc.date.issued2020
dc.description.abstractAt present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age > 60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled protein?protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 5? UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes. 2020, Indian Academy of Sciences.en_US
dc.identifier.doi10.1007/s12041-020-01217-7
dc.identifier.issn221333
dc.identifier.urihttp://10.2.3.109/handle/32116/2624
dc.identifier.urlhttps://link.springer.com/article/10.1007/s12041-020-01217-7
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.subjectcoronavirus disease-19en_US
dc.subjectdipeptidyl peptidase-4en_US
dc.subjectsevere acute respiratory syndrome coronavirus-2en_US
dc.subjectspike proteinen_US
dc.subjecttransmembrane protease serine 2en_US
dc.subjecttype-2 diabetesen_US
dc.titleAssessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in humanen_US
dc.title.journalJournal of Geneticsen_US
dc.typeArticleen_US
dc.type.accesstypeOpen Accessen_US

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