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Cytokine . FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children

tetano

Editor, Senior Moderator
Cytokine


. 2025 May 13:191:156958.
doi: 10.1016/j.cyto.2025.156958. Online ahead of print. FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children

Amal Ahmed Mohamed[SUP] 1 [/SUP], Abdullah Taher Alanazi[SUP] 2 [/SUP], Hoda H Ahmed[SUP] 3 [/SUP], Samar Elfiky[SUP] 4 [/SUP], Muhammad T Abdel Ghafar[SUP] 5 [/SUP], Ingy Maher[SUP] 6 [/SUP], Sherin A Taha[SUP] 7 [/SUP], Mohammed Zakaria Ali AbuRahma[SUP] 8 [/SUP], Waleed Elagawy[SUP] 9 [/SUP], Dina A Mohareb[SUP] 10 [/SUP], Abeer M Rawy[SUP] 11 [/SUP], Heba M Abostate[SUP] 12 [/SUP], Amira AlSayed Youssef[SUP] 13 [/SUP], Dalia Saeed Elsayed[SUP] 14 [/SUP], Rasha M Abdel-Hamid[SUP] 15 [/SUP]



Affiliations
Abstract

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.

Keywords: COVID-19; FokI polymorphism; Inflammatory biomarkers; Pediatric; Vitamin D receptor.

 
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