Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients

Abstract

Introduction Growing evidence documented the critical impacts of vitamin D (VD) in the prognosis of COVID-19 patients. The functions of VD are dependent on the vitamin D receptor (VDR) in the VD/VDR signaling pathway. Therefore, we aimed to assess the association of VDR gene polymorphisms with COVID-19 outcomes. Methods In the present study, eight VDR single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 500 COVID-19 patients in Iran, including 160 asymptomatic, 250 mild/moderate, and 90 severe/critical cases. The association of these polymorphisms with severity, clinical outcomes, and comorbidities were evaluated through the calculation of the Odds ratio (OR). Results Interestingly, significant associations were disclosed for some of the SNP-related alleles and/or genotypes in one or more genetic models with different clinical data in COVID-19 patients. Significant association of VDR-SNPs with signs, symptoms, and comorbidities was as follows: Apa I with shortness of breath (P ˂ 0.001) and asthma (P = 0.034) in severe/critical patients (group III); Bsm I with chronic renal disease (P = 0.010) in mild/moderate patients (group II); Tru9I with vomiting (P = 0.031), shortness of breath (P = 0.04), and hypertension (P = 0.030); Fok I with fever and hypertension (P = 0.027) in severe/critical patients (group III); CDX2 with shortness of breath (P = 0.022), hypertension (P = 0.036), and diabetes (P = 0.042) in severe/critical patients (group III); Eco RV with diabetes (P ˂ 0.001 and P = 0.045 in mild/moderate patients (group II) and severe/critical patients (group III), respectively). However, the association of VDR TaqI and Bgl I polymorphisms with clinical symptoms and comorbidities in COVID-19 patients was not significant. Conclusion VDR gene polymorphisms might play critical roles in the vulnerability to infection and severity of COVID-19, probably by altering the risk of comorbidities. However, these results require further validation in larger studies with different ethnicities and geographical regions.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID‐19

“…Bsm I was not related to disease severity in our study, but Abdollahzadeh et al 42 reported that the b allele was found to be a predisposition factor to COVID-19 severity.…”

“…In short, the f allele has affected the prognosis of subjects, and the FF genotype was mainly detected in subjects with a good prognosis, which can be a protective factor against ICU admission. In Abdollahzadeh et al's study, 42 Fok I f allele was also positively associated with signs, symptoms, and the severity of COVID‐19 affected people.…”

“…45 Th2 can also produce IL-6, which is related to COVID-19 prognosis 46 and may explain the higher death rate in subjects with aa genotype of Apa I polymorphism in our study. In Abdollahzadeh et al's study, 42 subjects with severe/critical and mild/ moderate disease who had "Aa" genotype compared to "AA+aa" genotypes had a rising severity risk. However, in symptomaticasymptomatic and mild/moderate-asymptomatic subjects with AA genotype made subjects more prone to possess signs and symptoms versus both "Aa+aa" and "Aa" genotypes.…”

“…Roth et al has shown that Taq I Tt genotype had a greater risk of acute lower respiratory infection than those with tt genotypes 18. In Abdollahzadeh et al's study,42 Taq I was not associated with clinical manifestations and severity of COVID-19. However, in our study, TT showed a poor prognosis for admission to ICU, and Tt was protective.…”

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“…It is a powerful modulator of the immune system [ 141 ], with antimicrobial functions [ 139 , 142 ]. VD exerts its functions through interaction with a nuclear vitamin D receptor (VDR) [ 143 ], in the VD/VDR signaling pathway [ 144 ]. This receptor is expressed in a wide variety of immune cells, influencing the secretion of cytokines and the function of different populations of lymphocytes [ 139 , 145 ].…”