Verma Shrikant, Verma Sushma, Siddiqi Zeba, Raza Syed Tasleem, Faruqui Tabrez, Ansari Asma Imran, Abbas Mohammad, Mahdi Farzana
Department of Personalized and Molecular Medicine, Era University, Lucknow, Uttar Pradesh, 226003, India.
Department of Medicine, Eras Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India.
Mol Biol Rep. 2025 Mar 19;52(1):327. doi: 10.1007/s11033-025-10417-2.
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.
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.
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.
新型冠状病毒肺炎（COVID-19）的表现从无症状到严重不等，并受宿主遗传因素影响。本研究检测了维生素D受体（VDR）基因多态性（TaqI和FokI）与跨膜丝氨酸蛋白酶2（TMPRSS2）基因多态性（rs12329760）和COVID-19严重程度之间的关联。
242例COVID-19患者采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。使用SPSS v.21和SHesis软件进行统计分析，并通过桑格测序进行验证。研究了VDR TaqI、FokI和TMPRSS2 rs12329760基因多态性与COVID-19严重程度的关联。利用TMPRSS2的计算分析来确定这些单核苷酸多态性（SNP）的致病性和结构效应。对于VDR TaqI，“TC”基因型在重症病例中的患病率（50.5%）高于轻症病例（41.4%）；然而，未观察到统计学上的显著关联[比值比（OR）：1.545（0.893 - 2.675），p＞0.05]。“CC”基因型和“C”等位基因也有类似模式，无统计学意义。对于VDR FokI，“Ff”基因型在重症病例中的患病率（25.8%）高于轻症病例（20.0%）[OR：0.766（0.199 - 2.951），p = 0.69]，无显著关联。单倍型分析中，重症病例中观察到“Tf”和“ft”单倍型频率升高，但无统计学意义。对于TMPRSS2 rs12329760，“CT”基因型在重症病例中的患病率（50.5%）略高于轻症病例（49.7%）[OR：0.805（0.276 - 2.345），p＞0.05]，无显著关联。计算分析表明该变异无致病性，但可能影响蛋白质稳定性。
本研究显示VDR（TaqI和FokI）和TMPRSS2（rs12329760）基因多态性与COVID-19严重程度之间无统计学上的显著关联。需要大规模调查和功能分析来阐明这些基因变异对COVID-19易感性和严重程度的影响。
