Transmembrane Serine Protease-2 Gene Polymorphism and Expression in Iraqi COVID-19 Patients

Abstract

The global COVID-19 pandemic was caused by SARS-CoV-2. Human cells ingest this virus when ACE2 identifies it. TMPRSS2 prepares SARS-CoV-2 for entry. The clinical outcomes of COVID-19 are associated with ACE2 and TMPRSS2 gene expression polymorphisms. Objective: To determine if the TMPRSS2 gene rs 2070788 SNP in intron 11-12 is associated with severe COVID-19 in Iraqi patients Methods: The study included 120 COVID-19 patients from three Ramadi City hospitals and 80 healthy controls. DNA extraction was done with Wizard genomic TM DNA Extraction Kit, RNA extraction was done with One Script Plus cDNA Synthesis Kit, and qRT-PCR was used for investigating genetic polymorphism.Results: The TMPRSS2 rs2070788 SNP had three genotypes (CC, CT, and TT) and two alleles. The genotypes of COVID-19 patients and controls were compatible with Hardy-Weinberg equilibrium (HWE). Severe COVID-19 patients and controls had significantly higher TT genotype frequencies in TMPRSS2 (28% vs 4%, OR = 9.33; 95% CI = 2.03 to 43.01; p = 0.002) and T allele (48% vs 16%, OR = 2.37; 95% CI = 1.32 to 4.26; p = 0.005), respectively. TMPRSS2 mRNA expression was much lower in severe cases than controls. In addition, the relative expression of TMPRSS2 mRNA was increased by 1.15 ± 0.71 folds in the CC genotype of rs2070788 SNP compared to the CT (0.632 ± 0.25) and TT (0.552 ± 0.193) genotypes, but the difference was not significant (p > 0.05). Conclusion:Iraqis were highly susceptible to COVID-19 due to the rs2070788 TT genotype and T allele. Severe cases also downregulated TMPRSS2 gene expression.