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      https://www.ias.ac.in/article/fulltext/jgen/099/0053

    • Keywords

       

      coronavirus disease-19; severe acute respiratory syndrome coronavirus-2; dipeptidyl peptidase-4; transmembrane protease serine 2; spike protein; type-2 diabetes

    • Abstract

       

      At 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 50 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.

    • Author Affiliations

       

      SABYASACHI SENAPATI1 SHASHANK KUMAR2 ATUL K. SINGH2 PRATIBHA BANERJEE1 SANDILYA BHAGAVATULA1

      1. Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda 151 001, India
      2. Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India
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