A strong association between the VDR gene markers and SARS-CoV-2 variants
Begimai Mamurova, Gokce Akan, Gulten Tuncel, Evren Mogol, Emine Unal Evren, Hakan Evren, Huseyin Kaya Suer, Tamer Sanlidag, Mahmut Cerkez Ergoren
doi:10.21203/rs.3.rs-1806260/v1
Introduction A COVID-19 disease, caused by the SARS-CoV-2, created signi cant 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 de ciency resulting from its low levels in COVID-19 patients. To our knowledge, there is no scienti c 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.
Methods The 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.
Results The 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). Signi cant 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 signi cant (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.
Conclusion Our results suggested that patients with FokI and TaqI polymorphisms might tend to be more susceptible to getting infected with the SARS-CoV-2. Overall, ndings from this study provided evidence regarding vitamin D supplements recommendation in individuals with vitamin D de ciency/insu ciency in the perior post-COVID-19 pandemic.
Declarations Ethical approval All procedures performed in this study were in accordance with the ethical standards the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (Approval number: YDU/202299-1451).
Con of Interest The authors do not have any con ict of interest to declare.
Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. Tables.docx
References
Abdollahzadeh, Shushizadeh, Barazandehrokh, Choopani, Azarnezhad et al., Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients. Infection, genetics, and evolution, journal of molecular epidemiology and evolutionary genetics in infectious diseases,
doi:10.1016/j.meegid.2021.105098Al-Anouti, Mousa, Karras, Grant, Alhalwachi et al., Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 UAE Residents, Nutrients2021,
doi:10.3390/nu13113680Annweiler, Corvaisier, Gautier, Dubée, Legrand et al., Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study, Nutrients,
doi:10.3390/nu12113377Apaydin, Polat, Dincer Yazan, Ilgin, Elbasan et al., Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19, Clinical endocrinology,
doi:10.1111/cen.14664Aranow, Carpagnano, Quaranta, Zito, Buonamico et al., Vitamin D de ciency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, Journal of endocrinological investigation,
doi:10.1007/s40618-020-01370-xCastillo, Entrenas Costa, Vaquero Barrios, Alcalá Díaz, López Miranda et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, The Journal of steroid biochemistry and molecular biology,
doi:10.1016/j.jsbmb.2020.105751Cevik, Kuppalli, Kindrachuk, Peiris, Virology, transmission, and pathogenesis of SARS-CoV-2, BMJ,
doi:10.1136/BMJ.m3862Charoenngam, Holick, Immunologic effects of vitamin D on human health and disease, Nutrients,
doi:10.3390/nu12072097Dror, Morozov, Daoud, Namir, Yakir, Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness, PLOS ONE,
doi:10.1371/journal.pone.0263069Freitas, Calhau, Antunes, Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity, Sci Rep,
doi:10.1038/s41598-021-99952-zGallagher, Covid: Is there a limit to how much worse variants can get?
Grant, Al Anouti, Boucher, Dursun, Gezen-Ak et al., A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health, Nutrients,
doi:10.3390/nu14030639Hendy, None
Holick, The vitamin D de ciency pandemic: approaches for diagnosis, treatment, and prevention, Rev Endocr Metab Disord
Ji, Wu, Qiu, Ming, Zhang et al., The Pathogenesis and Treatment of COVID-19: A System Review, Biomedical and environmental sciences: BES,
doi:10.3967/bes2021.007Kandemiş, Tuncel, Fahrioğlu, Temel, Mocan et al., Natural selection at work? Vitamin D de ciency rates and rising health problems in young Turkish Cypriot professionals, Central European Journal of public health,
doi:10.21101/cejph.a6117Kaufman, Ponga, Molecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations, Scienti c Reports
Krawiec, Dominiak, The role of vitamin D in the human body with a special emphasis on dental issues: A literature review, Dental and medical problems,
doi:10.17219/dmp/99051Laplana, Royo, Fibla, Vitamin D Receptor polymorphisms and risk of enveloped virus infection: a meta-analysis, Gene
Lee, Bae, Choi, Ji, Song, Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: A meta-analysis, Biol. Rep
Lee, Hsueh, Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV, J Microbiol Immunol Infect
Li, Wu, Liu, Yang, Vitamin D receptor gene polymorphisms and type 2 diabetes: A meta-analysis, Med. Res
Liu, Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to, Chim
Mamani, Muceli, Basir, Vasheghani, Poorolajal, Association between serum concentration of 25-hydroxyvitamin D and community-acquired pneumonia: a case-control study, Int J Gen Med
Martineau, Jolliffe, Greenberg, Aloia, Bergman et al., Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis, Health Technol Assess
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., None
Peralta, Rosales, Mesa, González, Pérez et al., TaqI polymorphism of the VDR gene: aspects related to the clinical behavior of COVID-19 in Cuban patients, The Egyptian Journal of Medical Human Genetics,
doi:10.1186/s43042-021-00206-4Raman, Patel, Ranjan, COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies, Biomolecules,
doi:10.3390/biom11070993Raoult, Zumla, Locatelli, Coronavirus infections: epidemiological, clinical and immunological features and hypotheses, Cell Stress
Rauf, Abu-Izneid, Olatunde, Ahmed Khalil, Alhumaydhi et al., COVID-19 Pandemic: Epidemiology, Etiology, Conventional and Non-Conventional Therapies, International journal of environmental research and public health,
doi:10.3390/ijerph17218155Shahhosseini, Babuadze, Giorgi, None
Tuncel, Temel, Ergoren, Strong association between VDR FokI (rs2228570) gene variant and serum vitamin D levels in Turkish Cypriots, Molecular biology reports,
doi:10.1007/s11033-019-04796-6Wang, Li, Lu, Huang, Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis, Aging12
Yi, Lagniton, Ye, Li, Xu, COVID-19: what has been learned and to be learned about the novel coronavirus disease, International journal of biological sciences,
doi:10.7150/ijbs.45134
