Association of VDR and TMPRSS2 gene polymorphisms with COVID-19 severity: a computational and clinical study.

Background: COVID-19 manifestations range from asymptomatic to severe, and are influenced by host genetic factors. This study examined the association between vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and transmembrane serine protease 2 (TMPRSS2) gene polymorphisms (rs12329760) and COVID-19 severity.

Methods And Results: 242 COVID-19 patients underwent genotyping using PCR-RFLP. Statistical analysis were conducted using SPSS v.21 and SHesis software, and validated by Sanger sequencing. The association of the VDR TaqI, FokI, and TMPRSS2 rs12329760 polymorphisms with COVID-19 severity was investigated. Computational analysis of TMPRSS2 was used to determine the pathogenicity and structural effects of these SNPs. For VDR TaqI, the 'TC' genotype showed higher prevalence in severe cases (50.5%) compared to mild cases (41.4%); however, no statistically significant association was observed [OR: 1.545 (0.893-2.675), p > 0.05]. Similar patterns were noted for the 'CC' genotype and 'C' allele, without statistical significance. For VDR FokI, the 'Ff' genotype showed higher prevalence in severe cases (25.8%) compared to mild cases (20.0%) [OR: 0.766 (0.199-2.951), p = 0.69], with no significant association. In haplotype analysis, elevated frequencies of 'Tf' and 'ft' haplotypes were observed in severe cases, but without statistical significance. For TMPRSS2 rs12329760, the 'CT' genotype showed a marginally higher prevalence in severe cases (50.5%) than in mild cases (49.7%) [OR: 0.805 (0.276-2.345), p > 0.05], without significant association. Computational analysis indicated that the variant does not demonstrate pathogenic effects but may influence protein stability.

Conclusion: This study revealed no statistically significant association between VDR (TaqI and FokI) and TMPRSS2 (rs12329760) polymorphisms and COVID-19 severity. Large-scale investigations and functional analysis are required to delineate the impact of these genetic variations on COVID-19 susceptibility and severity.