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. 2025 Mar 19;52(1):327.
doi: 10.1007/s11033-025-10417-2.

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

Shrikant Verma  1 , Sushma Verma  1 , Zeba Siddiqi  2 , Syed Tasleem Raza  3 , Tabrez Faruqui  1 , Asma Imran Ansari  1 , Mohammad Abbas  4   5 , Farzana Mahdi  1
Affiliations

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

Shrikant Verma et al. Mol Biol Rep. .

Abstract

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.

Keywords: TMPRSS2; VDR; COVID-19; Haplotype; SNPs; Severity.

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Conflict of interest statement

Declarations. Ethical approval: This study was conducted in accordance with institutional ethical guidelines for human subject research and. Consent to participate: Written informed consent was obtained from all study participants following a comprehensive explanation of the study’s objectives and potential benefits. Consent to publish: The authors affirmed that the human research participants provided informed consent for publication. Competing interests: The authors declare no competing interests.

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