The impact of TMPRSS11A rs353163 and rs977728 polymorphisms on COVID-19 severity: genotypic and clinical associations

COVID-19, caused by SARS-CoV-2, represents a significant global health challenge, with genetic factors influencing the severity of the disease. Transmembrane Serine Protease 11 A (TMPRSS11A) is a serine protease, and the relationship between the rs353163 and rs977728 polymorphisms in its coding region and COVID-19 severity has not been fully elucidated. In this context, we aimed to investigate the association between the TMPRSS11A rs353163 and rs977728 polymorphisms and the severity of COVID-19.

The study included 84 control participants, 80 patients with mild COVID-19 (MC-19), and 168 patients with severe COVID-19 (SC-19). Genotyping was conducted using the restriction fragment length polymorphism (RFLP) method. The genotype distributions, haplotype frequencies, and their relationships with clinical parameters were statistically analyzed.

This study investigated the impact of TMPRSS11A rs977728 C > T and rs353163 T > C polymorphisms on COVID-19 disease severity by examining their associations with genetic variations and clinical parameters. No homozygous mutant genotype was detected for the rs353163 T > C polymorphism. The heterozygous TC genotype was associated with a 3-fold increased risk of developing severe COVID-19 (OR = 3.300; p < 0.001). For the rs977728 C > T polymorphism, the TT and CT genotypes were observed at significantly higher frequencies in the SC‑19 group, corresponding to 7.6-fold and 2.3-fold increased risks, respectively. Haplotype analysis revealed that the rs977728 wild-type C / rs353163 mutant C* haplotype was strongly associated with SC‑19 disease severity. All genotype combinations carrying the mutant allele (rs977728 C > T / rs353163 T > C*) were associated with poor prognosis, as indicated by clinical parameters including CRP, D-dimer, ferritin, hs‑troponin, Neu, Neu%, Lym, Lym%, and Neu/Lym. ROC curve analysis identified CRP and D-dimer levels as sensitive markers for distinguishing the SC-19 group from other groups. Notably, the TT/TC* and CT/TC* genotype combinations were particularly associated with elevated CRP and D-dimer levels within the SC-19 group.

Carriers of the mutant alleles of TMPRSS11A rs977728 and rs353163 are thought to increase the risk of severe COVID‑19, in association with systemic inflammation, hypercoagulability, and organ damage.