Vitamin D and polymorphisms of VDR and GC genes in the severity and mortality from COVID-19. A systematic review

Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.