Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 infection severity

Abstract

Background: Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. Methods: This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. Results: The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.042). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). Conclusion: This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

“…A study which aimed to assess the association between variants in the GC gene that encodes vitamin D binding/transport protein (DBP), and the prevalence and mortality rates of COVID-19, pointed out to rs7041 variant (42). Another recent study (not peer-reviewed yet) performed in Portuguese population of COVID-19 patients found an association of GC rs2282679 variant with COVID-19 disease severity (43). Our study indicated an association between DHCR7/NADSYN1 rs12785878 and CYP2R1 rs10741657 variants and the severity of COVID-19, but the variants GC rs2282679 and VDR rs2228570 were not linked to a higher risk of severe COVID-19 in adults.…”

The potential significance of vitamin D binding protein polymorphism in COVID-19

“…Investigating the influence of the DBP phenotypes in patients with a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, we demonstrated that DBP1 carriers might be less susceptible to infection and mortality due to COVID-19 (Speeckaert et al, 2021). Besides, in a recent paper, a positive correlation was observed between the Metabolism score (= DBP rs2282679 + CYP24A1 rs17216707) and COVID-19 disease severity, in which a deeper analysis showed that the rs2282679 polymorphism could explain most of this interesting correlation (Freitas et al, 2021). Besides the transport of vitamin D and its metabolites, DBP could exert several other key roles in COVID-19, being involved in the extracellular actin scavenger system or acting as a neutrophil chemotactic factor and a macrophage activator (Delanghe et al, 2015).…”

Contribution of Vitamin D–Binding Protein Polymorphism to Susceptibility and Outcome of COVID-19 Patients

“…To support this statement, we have investigated in a previous report ( 6 ) the influence of the DBP phenotypes in patients with a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by comparing the frequency of the DBP1 allele (a mixture of DBP1F and DBP1S) with the prevalence and mortality data of COVID-19 in 55 countries. An association was observed between the DBP1 allele frequency and a lower prevalence and mortality due to a SARS-CoV-2 infection, which could be partly explained by the potential protective effects of vitamin D. In another study ( 7 ) that investigated the impact of patient genetic background related to vitamin D pathways on COVID-19 severity, the SNP rs2282679 could explain most of the positive correlation between the metabolism score (DBP rs2282679 + CYP24A1 rs17216707) and COVID-19 severity (ρ = 0.13, P value = 0.005) ( 7 ). Besides the DBP gene, the CYP2R1 gene (rs10741657), the CYP24A1 gene (rs6013897), and the DHCR7/NADSYN1 region (rs12785878) are also genetic determinants of the 25(OH)D concentration.…”

“…Besides the DBP gene, the CYP2R1 gene (rs10741657), the CYP24A1 gene (rs6013897), and the DHCR7/NADSYN1 region (rs12785878) are also genetic determinants of the 25(OH)D concentration. However, no association has been found between the vitamin D total score (DHCR7 rs12785878 + CYP2R1 rs10741657 + DBP rs2282679 + CYP24A1 rs17216707 + AMDHD1 rs10745742 + SEC23A rs8018720) and the severity of COVID-19 ( 7 ).…”