tetano
Editor, Senior Moderator
Mol Biol Rep
. 2025 Nov 5;53(1):51.
doi: 10.1007/s11033-025-11225-4. The impact of TMPRSS11A rs353163 and rs977728 polymorphisms on COVID-19 severity: genotypic and clinical associations
Nilgun Cekin[SUP] 1 [/SUP], Seyda Akin[SUP] 2 [/SUP], Ergun Pinarbasi[SUP] 2 [/SUP], Halef Okan Dogan[SUP] 3 [/SUP]
Affiliations
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: COVID-19; ECRG1; Polymorphism; Rs353163; Rs977728; Severity of disease; TMPRSS11A; Turkish population.
. 2025 Nov 5;53(1):51.
doi: 10.1007/s11033-025-11225-4. The impact of TMPRSS11A rs353163 and rs977728 polymorphisms on COVID-19 severity: genotypic and clinical associations
Nilgun Cekin[SUP] 1 [/SUP], Seyda Akin[SUP] 2 [/SUP], Ergun Pinarbasi[SUP] 2 [/SUP], Halef Okan Dogan[SUP] 3 [/SUP]
Affiliations
- PMID: 41191166
- DOI: 10.1007/s11033-025-11225-4
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: COVID-19; ECRG1; Polymorphism; Rs353163; Rs977728; Severity of disease; TMPRSS11A; Turkish population.