Role of FokI rs2228570 and Tru9I rs757343 Polymorphisms in the Mortality of Patients Infected with Different Variants of SARS-CoV-2

BACKGROUND AND AIM: Low vitamin D levels are associated with the severity of coronavirus disease 19 (COVID-19). Vitamin D receptor gene polymorphisms, such as Tru9I rs757343 and FokI rs2228570, have been suggested to be potential risk factors for severe COVID-19 outcomes. This study investigated how Tru9I rs757343 and FokI rs2228570 polymorphisms influenced the mortality rate of COVID-19 in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: The polymerase chain reaction-restriction fragment length polymorphism assay was used to genotype Tru9I rs757343 and FokI rs2228570 genotypes in 1,734 recovered and 1,450 deceased patients. RESULTS: Our results demonstrated that the high mortality rate was correlated with FokI rs2228570 TT genotype in all three variants but was much higher in the Omicron BA.5 variant than in the Alpha and Delta variants. Furthermore, in patients infected with the Delta variant, FokI rs2228570 CT genotype was more highly correlated with the mortality rate compared to other variants. Thus, a high mortality rate was correlated with the Tru9I rs757343 AA genotype in the Omicron BA.5 variant, whereas this relationship was not observed in the other two variants. The T-A haplotype was related to COVID-19 mortality in all three variants, but its effect was more pronounced in the Alpha variant. Moreover, the T-G haplotype was significantly associated with all three variants. CONCLUSION: Our findings showed that the effects of Tru9I rs757343 and FokI rs2228570 polymorphisms were related to SARS-CoV-2 variants. However, further studies are still required to validate our findings.