Association of Vitamin D Receptor (VDR) Gene Polymorphisms with COVID-19 Susceptibility in the Kurdistan Region

Coronavirus disease-2019 COVID-19 exhibits marked inter-individual variability in susceptibility and clinical outcomes, suggesting a role for host genetic factors. Vitamin D exerts immunomodulatory effects through the vitamin D receptor (VDR), and genetic variation in the VDR gene may influence host responses to SARS-CoV-2 infection. This study aimed to investigate the association between VDR-gene polymorphisms—FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232), and BsmI (rs1544410)—and COVID-19 susceptibility in the Kurdish population. The FokI polymorphism was significantly associated with COVID-19 susceptibility. Interestingly, the GG-genotype was more frequent among Patients than controls and was associated with increased odds of infection (OR = 9.00; 95% CI: 3.22–25.15; p < 0.0001), whereas the AG-genotype was associated with reduced susceptibility (OR = 0.33; 95% CI: 0.14–0.76; p = 0.001). Additionally, the G-allele was also more prevalent in Patients than controls (OR = 1.87; 95% CI: 1.21–2.89; p = 0.004). Similarly, the TaqI TT-genotype was more frequent among Patients and was associated with increased susceptibility (OR = 36.0; 95% CI: 11.2–115.8; p < 0.0001). In contrast, the ApaI AA-genotype was less frequent among Patients and was associated with reduced odds of COVID-19 susceptibility under a recessive model (OR = 0.15; 95% CI: 0.03–0.68; p = 0.003). Moreover, the BsmI polymorphism was monomorphic in both groups and therefore not informative. Genetic variation in the VDR gene, particularly at the FokI, TaqI, and ApaI loci, was associated with COVID-19 susceptibility in the case–control study, while BsmI showed no variations. These findings suggest that genetic variation in the VDR gene may contribute to inter-individual differences in susceptibility to SARS-CoV-2 infection in the Kurdish population. Larger studies incorporating functional validation and detailed clinical data are required to confirm these associations.