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Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence

Journal

BIOMEDICINES
Volume 11, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines11020400

Keywords

vitamin D; 25-hydroxyvitamin D; vitamin D receptor; vitamin D-binding protein; DBP; GC protein; COVID-19; SARS-CoV-2; polymorphism; genetic variation

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The activation of vitamin D receptor (VDR) has beneficial effects on mitigating the susceptibility and severity of COVID-19 infection. Vitamin D-binding protein (DBP) also affects the immune system and may influence inflammation associated with COVID-19. Low levels of serum 25-hydroxyvitamin D have been associated with increased risk and severity of COVID-19 infection. However, the effectiveness of vitamin D supplementation as a treatment for COVID-19 based on randomized clinical trials is still uncertain.
The immunomodulatory and metabolic effects of vitamin D receptor (VDR) activation have been considered beneficial in mitigating the susceptibility and severity of COVID-19 infection. Furthermore, vitamin D-binding protein (DBP) has pleiotropic effects on the immune system that may influence inflammation associated with COVID-19. Multiple observational studies have demonstrated an association between low levels of serum 25-hydroxyvitamin D and risk and the severity of COVID-19 infection. However, the impact of vitamin D supplementation as an adjunctive treatment for COVID-19 based on evidence from randomized clinical trials is unclear. Equally important is that certain variations of the genes involved in the vitamin D metabolic pathway have been shown to affect immune function and linked with various clinical outcomes, including cardio-metabolic disorders, autoimmune diseases, infections, and cancers. This indicates inter-individual difference in body response to vitamin D. There is also emerging evidence that common polymorphisms of these genes may influence the susceptibility and severity of COVID-19, although the confidence of these findings is limited by a small number of studies and participants. Further studies are needed to address the potential role of VDR activation and DBP in the pathophysiology of COVID-19 which take into account the genetic variations of vitamin D metabolic pathway.

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