A strong association between the VDR gene markers and SARS-CoV-2 variants

Abstract

IntroductionA COVID-19 disease, caused by the SARS-CoV-2, 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 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.MethodsThe nasopharyngeal swabs were taken from a total number of 600 patients who were admitted to Near East University Hospital COVID-19 PCR Diagnosis Laboratory for routine SARS-CoV-2 RT-qPCR test. The RT-qPCR negative resulting samples were taken as control samples (n = 300). On the other hand, 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 PCR-RFLP.ResultsThe mean age of the COVID-19 patient’s ± SD 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 (OR = 1.80, 95% 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.ConclusionOur results suggested that patients with FokI and TaqI polymorphisms might tend to be more susceptible to getting infected with the 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.

Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence

“…A number of observational studies have evaluated the association between vitamin D-related polymorphisms and risk of COVID-19 infection and severity [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116]. As shown in Table 1, most studies are from European and Middle eastern countries and included a relatively small number of participants.…”

“…Six retrospective cohort studies from Turkey, Iran, Portugal, United Arab Emirates, Serbia, and Cuba investigated the association between vitamin D-related polymorphisms and COVID-19 severity [102][103][104][105][106][107]. Four case-control studies from Italy, Iran, and Cyprus reported the association between VDR polymorphism and COVID-19 susceptibility [108][109][110][111], while one study from Iran reported the association between VDR polymorphism and COVID-19 mortality [112].…”

“…As shown in Table 2, VDR polymorphisms including FokI (rs2228570, exon 2, C > T), TaqI (rs731236, exon 9, A > G) and BsmI (rs1544410, intron 8, G > A) were shown to be associated with the risk of COVID-19 and severity in more than one observational study [102,103,[108][109][110][111][112]. However, the data from these studies are largely conflicting and inconclusive.…”