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

Abstract

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. 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. 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 = 0.04). 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%). 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.Trial registration: NCT04370808.

Potential Genes Associated with COVID-19 and Comorbidity

“…Recent studies have shown that 25(OH)D levels are related to mortality from COVID-19. The GC variant of rs2282679 in the gene encoding a vitamin D binding protein is associated with disease severity, and the DHCR7 rs12785878 variant associated with vitamin D deficiency has a higher prevalence in the Portuguese population than in Europe and may explain more severity of COVID-19 in the Portuguese population 102 . Some scholars have suggested that using the combination of dexamethasone and vitamin D in COVID-19 may improve the symptom of ARDS 103 .…”

Vitamin D receptor gene polymorphism predicts left ventricular hypertrophy in maintenance hemodialysis

“…However, Although VDBP polymorphisms can induce the severity of infection [ 27 , 28 ], there is no strong evidence of an impact on CVD, because VDBP level is associated neither with disease outcome nor with vitamin D status. The GC gene variant also has no effect on 25(OH) D levels [ 29 – 32 ].…”

Commentary: Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity

“…This finding could be partly explained by the potential protective effects of vitamin D, as described in the paper of Vanegas-Cedillo et al ( 1 ). In another study, polymorphisms in the DBP gene were also related to the infection severity of COVID-19 ( 7 ). The vitamin D total risk score ( DHCR7 ; CYP2R1 ; DBP ; CYP24A1 ; AMDHD1 ; SEC23A ) was associated with the serum 25OHD concentration.…”