Association between vitamin D polymorphisms and binding protein and COVID-19 risk and severity in children

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BACKGROUND: The effects of genetic background on the biological effects of vitamin D on coronavirus disease 2019 (COVID-19) in children remain unclear. PURPOSE: This study aimed to explore the association between vitamin D-related genetic background and 25-hydroxyvitamin D status and COVID-19 occurrence and severity in children. Here we explored key genetic variants within the vitamin D pathway in pediatric COVID-19 patients in relation to circulating vitamin D binding protein (VDBP). METHODS: Sixty children aged 0-14 years with severe acute respiratory syndrome coronavirus 2 infection and 60 matched controls were genotyped for the vitamin D receptor (VDR) gene (FokI, BsmI, TaqI, ApaI), Gc gene of VDBP (rs7041, rs4588), and CYP27B1 promoter (rs10877012) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism assay. RESULTS: The FokI FF genotype was more frequently identified among COVID-19 patients than controls, among whom the TaqI TT genotype was prevalent (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.08-4.73; P=0.02; and OR, 0.29; 95% CI, 0.13-0.63; P=0.001, respectively). The Gc1F haplotype was significantly more represented in controls versus COVID-19 patients (OR, 0.39; 95% CI, 0.19-0.81; P=0.01). A 2.04-fold increased risk of COVID-19 was observed in the presence of the VDR FokI F allele (OR, 2.04; 95% CI, 1.14-3.64; P=0.01). A multivariate analysis revealed a significant association between the FokI FF genotype and disease severity (OR, 0.20; 95% CI, 0.04-0.83; P=0.02). Serum VDBP levels were similar between groups. CONCLUSION: The FF genotype of the VDR FokI polymorphism may be associated with COVID-19 and have a significant clinical impact on disease severity in children.

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