Strong Association between Vitamin D Receptor Gene and Severe Acute Respiratory Syndrome coronavirus 2 Infectious Variants

Abstract

A coronavirus disease 2019 (COVID-19) disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created significant concern since December 2019 worldwide. The virus is known to be highly transmissible. Heterogenic clinical features even vary more among SARS-CoV-2 variants from asymptomatic forms to severe symptoms. Previous studies revealed an association between COVID-19 and vitamin D deficiency resulting from its low levels in COVID-19 patients. To our knowledge, there is no scientific investigation that evaluates the direct association between SARS-CoV-2 variants of concern and vitamin D receptor (VDR) gene markers in Cyprus. Thus, the present study aimed to identify the putative impact of VDR gene polymorphisms on SARS-CoV-2 infection among different variants.
The nasopharyngeal swabs were taken from a total number of 600 patients who were admitted to Near East University Hospital COVID-19 Polymerase Chain Reaction (PCR) Diagnosis Laboratory for routine SARS-CoV-2 real-time quantitative reverse transcription PCR (RT-qPCR) test. The RT-qPCR negative resulting samples were taken as control samples (n = 300). On the contrary, the case group consisted of patients who were SARS-CoV-2 RT-qPCR positive, infected with either SARS-CoV-2 Alpha (n = 100), Delta (n = 100), or Omicron (n = 100) variants. Two VDR gene polymorphisms, TaqI-rs731236 T > C and FokI-rs10735810 C > T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism.
The mean age of the COVID-19 patient's ± standard deviation was 46.12 ± 12.36 and 45.25 ± 12.71 years old for the control group (p > 0.05). The gender distribution of the patient group was 48.3% female and 51.7% male and for the control group 43% female and 57% male (p > 0.05). Significant differences were observed in genotype frequencies of FokI and TaqI variants between SARS-CoV-2 patients compared to the control group (p < 0.005). Furthermore, the risk alleles, FokI T allele and TaqI C, were found to be statistically significant (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.42-2.29, OR = 1.62, 95% CI = 1.27-2.05, respectively) in COVID-19 patients. The highest number of patients with wild-type genotype was found in the control group, which is 52.9% compared with 17.5% in the case group. Moreover, most of the COVID-19 patients had heterozygous/homozygous genotypes, reaching 82.5%, while 47.1% of the control group patients had heterozygous/homozygous genotypes.
Our results suggested that patients with FokI and TaqI polymorphisms might tend to be more susceptible to getting infected with SARS-CoV-2. Overall, findings from this study provided evidence regarding vitamin D supplements recommendation in individuals with vitamin D deficiency/insufficiency in the peri- or post-COVID-19 pandemic.

Keywords

COVID-19 / VDR / polymorphism / FokI / TaqI

Ethical Approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (Approval number: YDU/202299-1451).

Data Availability Statement

The data is available upon request.

Author Contribution

G.A. and M.C.E. conceived and designed the analysis; B.M., G.A., G.T., E.M., A.T., E.U.E., H.E., H.K.S., and M.C.E. collected the data; B.M., G.A., G.T., E.M., E.U.E., H.E., H.K.S., and M.C.E. contributed data or analysis tools; B.M., G.A., G.T., and E.M. performed the analysis; B.M. and G.A. wrote the paper; B.M., G.A., G.T., E.M., E.U.E., H.E., H.K.S., T.S., and M.C.E. revised the paper; M.C.E. supervised the project.

Funding

None.

Conflict of Interest

None declared.

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Global Medical Genetics