Single nucleotide variants rs7975232 and rs2228570 within vitamin D receptor gene confers protection against severity of COVID-19 infection in Bangladeshi population

Abstract

Vitamin D insufficiency has been linked to an elevated susceptibility to SARS CoV-2 infection in several studies owing to its immunomodulatory properties. This study aimed to examine the association between vitamin D levels and the genetic variations in the vitamin D receptor (VDR) gene with the severity of COVID-19. A total of 71 COVID-19 patients (Mild = 27, Moderate = 20, Severe = 24) and healthy individuals (n = 22) were recruited in this study. The 25 (OH) vitamin D level was found to be lowest in the severe COVID-19 patients (18.2 ng/mL) compared to other study participants. Initially, Whole Exome Sequencing (WES) of 29 individuals was conducted (patients, n = 22 and controls, n = 7) to identify potential mutational hotspots within the VDR gene. The WES data revealed 2 exonic and 10 intronic variants in the VDR region of the study participants. Further analysis included large number of samples comprising 64 individuals to evaluate the association of 3 SNPs, rs11168266, rs7975232, and rs2228570, with the disease severity employing Sanger sequencing or PCR-RFLP. The genotype T/T [OR (95%CI): 0.32 (0.13–0.79), p = 0.013] and genotype C/C [OR (95%CI): 0.36 (0.15–0.89), p = 0.02] of rs7975232 and rs2228570, respectively were found to be significantly associated with lower risk of COVID-19 severity under recessive model. In conclusion, the genotypes T/T and C/C of ApaI and FokI confer protection against severe COVID-19 in Bangladeshi population, which warrants further validation in a larger sample size.