Vitamin D Deficiency and Receptor Polymorphisms as Risk Factors for COVID-19
Nur Efe Iris, Ozlem Akman, Demet Akin, Palmet Gun Atak, Ahmed Cihad Genc, Funda Simsek, Taner Yildirmak, Gunnur Demircan
Jundishapur Journal of Microbiology, doi:10.5812/jjm-140726
Background: Early immune responses to COVID-19 can help eliminate the virus; therefore, strategies to improve the immune system have become important in disease prevention. Vitamin D plays a crucial role in the immune response to SARS-CoV-2 by increasing the expression of the vitamin D receptor. Objectives: This study investigated the impact of vitamin D deficiency, Fok 1, and Taq 1 Vitamin D Receptor (VDR) gene polymorphisms and comorbidities on the susceptibility to COVID-19. Methods: Fok1 and Taq1 polymorphisms were analyzed using the RT-PCR method, and vitamin D levels were measured using the chemiluminescence method. A total of 200 patients, 100 with COVID-19 and 100 without, provided blood samples for analysis.
Results: The COVID-19 positive group had a significantly lower mean vitamin D level of 16.2 ± 11.3 ng/mL compared to the COVID-19 negative control group, 26.7 ± 15.9 ng/mL (P < 0.001). Individuals with a vitamin D level below 18.4 ng/mL had a 2.448 times higher risk of COVID-19 positivity (P < 0.001). There was no significant difference in the Fok1 and Taq1 gene polymorphisms between the two groups. (P = 0.548 and P = 0.098). The COVID-19 positive group had a significantly higher number of comorbid diseases with 40 (40%) compared to the negative group with 10 (10%) participants (P < 0.001). Conclusions: Levels of vitamin D above the cut-off value of 18.4 ng/mL were found to protect against COVID-19, while the presence of comorbid diseases was identified as a risk factor. However, no association was observed between the Fok1 and Taq1 polymorphisms and susceptibility to COVID-19.
Conflict of Interests: The authors assert that there are no conflicts of interest. Data Reproducibility: It was not declared by the authors.
Ethical Approval: This study has been approved under the ethical approval code 04.08.2020/2020-14-02 Demiro glu Bilim University Ethical Committee. Funding/Support: Researchers supported the study with their own budget. Informed Consent: Informed consent was obtained from all participants.
References
Abdollahi, Sarvestani, Rafat, Ghaderkhani, Mahmoudi-Aliabadi et al., The association between the level of serum 25(OH) vitamin D, obesity, and underlying diseases with the risk of developing COVID-19 infection: A case-control study of hospitalized patients in Tehran, Iran, J Med Virol,
doi:10.1002/jmv.26726Abdollahzadeh, Shushizadeh, Barazandehrokh, Choopani, Azarnezhad et al., Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients, Infect Genet Evol,
doi:10.1016/j.meegid.2021.105098Akbar, Wibowo, Pranata, Setiabudiawan, Low serum 25-hydroxyvitamin D (vitamin D) level is associated with susceptibility to COVID-19, severity, and mortality: A systematic review and meta-analysis, Front Nutr,
doi:10.3389/fnut.2021.660420Basaran, Adas, Gokden, Turgut, Yildirmak et al., The relationship between vitamin D and the severity of COVID-19, Bratisl Lek Listy,
doi:10.4149/BLL_2021_034Bassatne, Basbous, Chakhtoura, El Zein, Rahme et al., The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis, Metabolism,
doi:10.1016/j.metabol.2021.154753Batur, Correlation of the variations in prevalence of coronavirus disease 2019 and vitamin D receptor gene polymorphisms in cohorts from 26 countries, Anadolu Klin Tıp Bilim Derg,
doi:10.21673/anadoluklin.987578Berry, Hesketh, Power, Hypponen, Vitamin D status has a linear association with seasonal infections and lung function in British adults, Br J Nutr,
doi:10.1017/S0007114511001991D'avolio, Avataneo, Manca, Cusato, Nicolo et al., 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359Ejaz, Alsrhani, Zafar, Javed, Junaid et al., COVID-19 and comorbidities: Deleterious impact on infected patients, J Infect Public Health,
doi:10.1016/j.jiph.2020.07.014Gombart, Pierre, Maggini, A review of micronutrients and the immune system-working in harmony to reduce the risk of infection, Nutrients,
doi:10.3390/nu12010236Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Holick, The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention, Rev Endocr Metab Disord,
doi:10.1007/s11154-017-9424-1Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8Jeffery, Burke, Mura, Zheng, Qureshi et al., 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3, J Immunol,
doi:10.4049/jimmunol.0803217Mccartney, Byrne, Optimisation of vitamin D status for enhanced immuno-protection against covid-19, Ir Med J
Murdaca, Pioggia, Negrini, Vitamin D and covid-19: an update on evidence and potential therapeutic implications, Clin Mol Allergy,
doi:10.1186/s12948-020-00139-0Ou, Jiang, Guan, Vitamin D receptor gene polymorphisms and risk of atopic dermatitis in chinese han population, Int J Gen Med,
doi:10.2147/IJGM.S326477Peralta, Rosales, Mesa, González, Pérez et al., TaqI polymorphism of the VDR gene: aspects related to the clinical behavior of COVID-19 in Cuban patients, Egypt J Med Hum Genet,
doi:10.1186/s43042-021-00206-4Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D deficiency and outcome of COVID-19 patients, Nutrients,
doi:10.3390/nu12092757Raisi-Estabragh, Mccracken, Bethell, Cooper, Cooper et al., Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank, J Public Health (Oxf),
doi:10.1093/pubmed/fdaa095Santos, Mascarenhas, Satler, Boguszewski, Spritzer, Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants, BMC Pediatr,
doi:10.1186/1471-2431-12-62Sharifi, Vahedi, Nedjat, Rafiei, Hosseinzadeh-Attar, Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo-controlled trial, APMIS,
doi:10.1111/apm.12982Ulucan, Akyuz, Ozbay, Pekiner, Guney, Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta, Tsitol Genet
Ye, Tang, Liao, Shaw, Deng et al., Does serum vitamin D level affect COVID-19 infection and its severity?-A case-control study, J Am Coll Nutr,
doi:10.1080/07315724.2020.1826005Zeidan, Lateef, Selim, Razek, Abd-Elrehim et al., Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19, Pediatr Res,
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'abstract': '<jats:p>Background: Early immune responses to COVID-19 can help eliminate the virus; '
'therefore, strategies to improve the immune system have become important in disease '
'prevention. Vitamin D plays a crucial role in the immune response to SARS-CoV-2 by increasing '
'the expression of the vitamin D receptor. Objectives: This study investigated the impact of '
'vitamin D deficiency, Fok 1, and Taq 1 Vitamin D Receptor (VDR) gene polymorphisms and '
'comorbidities on the susceptibility to COVID-19. Methods: Fok1 and Taq1 polymorphisms were '
'analyzed using the RT-PCR method, and vitamin D levels were measured using the '
'chemiluminescence method. A total of 200 patients, 100 with COVID-19 and 100 without, '
'provided blood samples for analysis. Results: The COVID-19 positive group had a significantly '
'lower mean vitamin D level of 16.2 ± 11.3 ng/mL compared to the COVID-19 negative control '
'group, 26.7 ± 15.9 ng/mL (P < 0.001). Individuals with a vitamin D level below 18.4 ng/mL '
'had a 2.448 times higher risk of COVID-19 positivity (P < 0.001). There was no significant '
'difference in the Fok1 and Taq1 gene polymorphisms between the two groups. (P = 0.548 and P = '
'0.098). The COVID-19 positive group had a significantly higher number of comorbid diseases '
'with 40 (40%) compared to the negative group with 10 (10%) participants (P < 0.001). '
'Conclusions: Levels of vitamin D above the cut-off value of 18.4 ng/mL were found to protect '
'against COVID-19, while the presence of comorbid diseases was identified as a risk factor. '
'However, no association was observed between the Fok1 and Taq1 polymorphisms and '
'susceptibility to COVID-19.</jats:p>',
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