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FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children
Cytokine . 2025 Jul:191:156958. doi: 10.1016/j.cyto.2025.156958 partial PDF on-line
Amal Ahmed Mohamed 1, Abdullah Taher Alanazi 2, Hoda H Ahmed 3, Samar Elfiky 4, Muhammad T Abdel Ghafar 5, Ingy Maher 6, Sherin A Taha 7, Mohammed Zakaria Ali AbuRahma 8, Waleed Elagawy 9, Dina A Mohareb 10, Abeer M Rawy 11, Heba M Abostate 12, Amira AlSayed Youssef 13, Dalia Saeed Elsayed 14, Rasha M Abdel-Hamid 15
Background: Vitamin D receptor (VDR), influenced by gene polymorphisms like FokI, may affect susceptibility to infections, including coronavirus disease 2019 (COVID-19). Since studies in children are limited, we aimed to analyze the correlation between the VDR FokI variant and both the incidence and severity of COVID-19 in Egyptian children.
Methods: Seventy-seven COVID-19-positive and 107 COVID-19-negative pediatric patients were included. Participants' serum 25(OH)D levels, inflammatory biomarkers, and demographics were evaluated. Real-time polymerase chain reaction (PCR) was used for genotyping the VDR FokI (rs2228570) polymorphism.
Results: Absolute lymphocyte count (ALC) was significantly lower in COVID-19 patients than in controls, while interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and D-dimer were significantly higher (all p < 0.001). Vitamin D insufficiency was significantly more common in COVID-19 cases (18.2 % versus 3.7 %, p = 0.002). Male sex, increased tumor necrosis factor-alpha (TNF-α), and CRP were significantly associated with severe COVID-19 (p = 0.032, 0.029, < 0.001, respectively).
The FokI TT genotype in codominant and recessive models and the T allele in the multiplicative model were significantly correlated with 2.4, 3.0, and 1.8 folds increased COVID-19 risk (p = 0.043, < 0.001, and 0.004, respectively). However, VDR FokI variants did not significantly associate with severe COVID-19.
Conclusion: The T allele and TT genotype of the FokI variant in the VDR gene increase susceptibility to COVID-19 but not its severity in Egyptian children. Additional research is required to validate the potential role of vitamin D and its receptor polymorphism in COVID-19