Plasma 25-Hydroxyvitamin D Level and VDR Gene Single Nucleotide Polymorphism rs2228570 Influence on COVID-19 Susceptibility among the Kazakh Ethnic Group—A Pilot Study
Valeriya V Protas, Gayane P Pogossyan, Konstantin G Li, Assel G Zhumina, Anar K Bisseneva, Dinara N Shaikina
Nutrients, doi:10.3390/nu15071781
Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated with the body's susceptibility to infectious diseases, including COVID-19. In this pilot retrospective study, representatives of the Kazakh population (central Kazakhstan) were divided into groups based on the test for IgM and IgG for coronavirus infection. We compared the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL ± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time PCR assay. Allele C predominated among the COVID-19-negative participants and significantly reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI 0.02357-0.2798). There were no statistically significant differences in the frequencies of the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ 2 = 5.364; OR = 4.131; 95% CI 1. 223-13.71). Comprehensive studies are required to determine whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for COVID-19 infection.
19, while the GG genotype increased these odds. Further studies on specific groups with a larger sample size and complete data in the Kazakh population are required.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu15071781/s1, Table S1 : Characteristics of study participants; Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
References
Abdollahzadeh, 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.2021.105098
Alagarasu, Honap, Mulay, Bachal, Shah et al., Association of Vitamin D Receptor Gene Polymorphisms with Clinical Outcomes of Dengue Virus Infection, Hum. Immunol,
doi:10.1016/j.humimm.2012.08.007
Ali, Role of Vitamin D in Preventing of COVID-19 Infection, Progression and Severity, J. Infect. Public Health
Alquaiz, Kazi, Fouda, Alyousefi, Age and Gender Differences in the Prevalence and Correlates of Vitamin D Deficiency, Arch. Osteoporos,
doi:10.1007/s11657-018-0461-5
Alvarez, Marson, Bertuzzo, Bastos, Baracat et al., Association between Single Nucleotide Polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 Genes with Acute Viral Bronchiolitis, Gene,
doi:10.1016/j.gene.2017.12.022
Apaydin, Polat, Dincer Yazan, Ilgin, Elbasan et al., Effects of Vitamin D Receptor Gene Polymorphisms on the Prognosis of COVID-19, Clin. Endocrinol
Bakaloudi, Chourdakis, A Critical Update on the Role of Mild and Serious Vitamin D Deficiency Prevalence and the COVID-19 Epidemic in Europe, Nutrition,
doi:10.1016/j.nut.2021.111441
Baturin, Sorokina, Vrzhesinskaya, Beketova, Sokolnikov et al., The study of the association between rs2228570 polymorphism of VDR gene and vitamin D blood serum concentration in the inhabitants of the Russian Arctic, Vopr. Pitan,
doi:10.24411/0042-8833-2017-00062
Bergman, Lindh, Björkhem-Bergman, Lindh, Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, PLoS ONE,
doi:10.1371/journal.pone.0065835
Biesalski, Vitamin D Deficiency and Co-Morbidities in COVID-19 Patients-A Fatal Relationship?, NFS J
Bradley, Schloss, Brown, Celis, Finnell et al., The Effects of Vitamin D on Acute Viral Respiratory Infections: A Rapid Review, Adv. Integr. Med,
doi:10.1016/j.aimed.2020.07.011
Böger, Fachi, Vilhena, Cobre, Tonin et al., Systematic Review with Meta-Analysis of the Accuracy of Diagnostic Tests for COVID-19, Am. J. Infect. Control,
doi:10.1016/j.ajic.2020.07.011
Chandran, Chan Maung, Mithal, Parameswaran, Vitamin D in COVID-19: Dousing the Fire or Averting the Storm?-A Perspective from the Asia-Pacific, Osteoporos. Sarcopenia,
doi:10.1016/j.afos.2020.07.003
D'avolio, Avataneo, Manca, Cusato, De Nicolò et al., 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359
Das, Bhanushali, Lajpal, Kulkarni, Chavan et al., Frequency of FokI and TaqI Polymorphism of Vitamin D Receptor Gene in Indian Population and Its Association with 25-Hydroxyvitamin D Levels, Indian J. Hum. Genet
Divanoglou, Komninou, Stea, Argiriou, Papatzikas et al., Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin D Levels in a Greek Rural Population (Velestino Study), Lifestyle Genom,
doi:10.1159/000514338
Gallelli, Mannino, Luciani, De Sire, Mancuso et al., Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study, Nutrients,
doi:10.3390/nu13113932
Gromova, Doschanova, Lokshin, Tuletova, Grebennikova et al., Vitamin D Deficiency in Kazakhstan: Cross-Sectional Study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2019.105565
Hashemi, Thijssen, Hosseini, Tabarraei, Pourkarim et al., Human Gene Polymorphisms and Their Possible Impact on the Clinical Outcome of SARS-CoV-2 Infection, Arch. Virol,
doi:10.1007/s00705-021-05070-6
Hassan, Bhat, Majid, Sajad, Rasool et al., Association of Vitamin D Receptor Gene Polymorphisms and Serum 25-Hydroxy Vitamin D Levels in Vitiligo-A Case-Control Study, Indian Dermatol. Online J,
doi:10.4103/idoj.IDOJ_97_18
Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D Concentrations and COVID-19 Infection in UK Biobank, Diabetes Metab. Syndr. Clin. Res. Rev,
doi:10.1016/j.dsx.2020.04.050
Israel, Cicurel, Feldhamer, Stern, Dror et al., Deficiency Is Associated with Higher Risks for SARS-CoV-2 Infection and COVID-19 Severity: A Retrospective Case-Control Study, Intern. Emerg. Med,
doi:10.1007/s11739-021-02902-w
Jafarpoor, Jazayeri, Bokharaei-Salim, Ataei-Pirkooh, Ghaziasadi et al., VDR Gene Polymorphisms Are Associated with the Increased Susceptibility to COVID-19 among Iranian Population: A Case-control Study, Int. J. Immunogenet,
doi:10.1111/iji.12585
Jayawardena, Jeyakumar, Francis, Misra, Impact of the Vitamin D Deficiency on COVID-19 Infection and Mortality in Asian Countries, Diabetes Metab. Syndr. Clin. Res. Rev,
doi:10.1016/j.dsx.2021.03.006
Kaufman, Niles, Kroll, Bi, Holick, SARS-CoV-2 Positivity Rates Associated with Circulating 25-Hydroxyvitamin D Levels, PLoS ONE,
doi:10.1371/journal.pone.0239252
Kotur, Skakic, Klaassen, Gasic, Zukic et al., Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity, Front. Nutr,
doi:10.3389/fnut.2021.689419
Kresfelder, Janssen, Bont, Venter, Confirmation of an Association between Single Nucleotide Polymorphisms in the VDR Gene with Respiratory Syncytial Virus Related Disease in South African Children, J. Med. Virol
Kumar, Rathi, Haq, Wimalawansa, Sharma, Putative Roles of Vitamin D in Modulating Immune Response and Immunopathology Associated with COVID-19, Virus Res,
doi:10.1016/j.virusres.2020.198235
Lagunova, Porojnicu, Lindberg, Hexeberg, Moan, The Dependency of Vitamin D Status on Body Mass Index, Gender, Age and Season, Obes. Metab,
doi:10.14341/2071-8713-4886
Li, Huang, Wang, Wang, Liang et al., COVID-19 Patients' Clinical Characteristics, Discharge Rate, and Fatality Rate of Meta-analysis, J. Med. Virol,
doi:10.1002/jmv.25757
Li, Shi, Yang, Li, Liu et al., The Association of Vitamin D Receptor Gene Polymorphisms and Serum 25-Hydroxyvitamin D Levels with Generalized Vitiligo: Association of VDR Polymorphisms and Vitiligo Risk, Br. J. Dermatol,
doi:10.1111/j.1365-2133.2012.11132.x
Luo, Liu, Li, Zheng, Ai et al., Dynamic Changes and Prevalence of SARS-CoV-2 IgG/IgM Antibodies: Analysis of Multiple Factors, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2021.04.078
Merzon, Tworowski, Gorohovski, Vinker, Golan Cohen et al., Low Plasma 25(OH) Vitamin D Level Is Associated with Increased Risk of COVID-19 Infection: An Israeli Population-based Study, FEBS J,
doi:10.1111/febs.15495
Mohammad, Alourfi, Haddad, Relationship between Vitamin D Receptor Gene FokI Polymorphism and 25-Hydroxyvitamin D Levels in Apparently Healthy Syrians, Meta Gene,
doi:10.1016/j.mgene.2021.100945
Mukherjee, Gorohovski, Merzon, Levy, Mukherjee et al., Seasonal UV Exposure and Vitamin D: Association with the Dynamics of COVID-19 Transmission in Europe, FEBS Open Biol,
doi:10.1002/2211-5463.13309
Muscogiuri, Barrea, Somma, Laudisio, Salzano et al., Sex Differences of Vitamin D Status across BMI Classes: An Observational Prospective Cohort Study, Nutrients
Nabih, Kamel, Association between Vitamin D Receptor Gene FokI Polymorphism and Atopic Childhood Bronchial Asthma. Egypt, J. Chest Dis. Tuberc,
doi:10.1016/j.ejcdt.2014.02.012
Nimavat, Singh, Singh, Singh, Sinha, Vitamin D Deficiency and COVID-19: A Case-Control Study at a Tertiary Care Hospital in India, Ann. Med. Surg,
doi:10.1016/j.amsu.2021.102661
Orces, The Association between Body Mass Index and Vitamin D Supplement Use among Adults in the United States, Cureus,
doi:10.7759/cureus.5721
Padhi, Suvankar, Panda, Pati, Panda, Lower Levels of Vitamin D Are Associated with SARS-CoV-2 Infection and Mortality in the Indian Population: An Observational Study, Int. Immunopharmacol,
doi:10.1016/j.intimp.2020.107001
Pike, Meyer, The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3, Endocrinol. Metab. Clin. N. Am,
doi:10.1016/j.ecl.2010.02.007
Silva-Ramírez, Saenz-Saenz, Bracho-Vela, Peñuelas-Urquides, Mata-Tijerina et al., Association between Vitamin D Receptor Gene Polymorphisms and Pulmonary Tuberculosis in a Mexican Population, Indian J. Tuberc,
doi:10.1016/j.ijtb.2018.04.005
Singh, Kaur, Singh, Revisiting the Role of Vitamin D Levels in the Prevention of COVID-19 Infection and Mortality in European Countries Post Infections Peak, Aging Clin. Exp. Res,
doi:10.1007/s40520-020-01619-8
Soltani-Zangbar, Mahmoodpoor, Dolati, Shamekh, Valizadeh et al., Serum Levels of Vitamin D and Immune System Function in Patients with COVID-19 Admitted to Intensive Care Unit, Gene Rep,
doi:10.1016/j.genrep.2022.101509
Song, Kim, Lee, Ham, Oh et al., Dynamics of Viral Load and Anti-SARS-CoV-2 Antibodies in Patients with Positive RT-PCR Results after Recovery from COVID-19, Korean J. Intern. Med,
doi:10.3904/kjim.2020.325
Teymoori-Rad, Marashi, Vitamin D and Covid-19: From Potential Therapeutic Effects to Unanswered Questions, Rev. Med. Virol,
doi:10.1002/rmv.2159
To, Tsang, Leung, Tam, Wu et al., Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody Responses during Infection by SARS-CoV-2: An Observational Cohort Study, Lancet Infect. Dis,
doi:10.1016/S1473-3099(20)30196-1
Urashima, Segawa, Okazaki, Kurihara, Wada et al., Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza A in Schoolchildren, Am. J. Clin. Nutr,
doi:10.3945/ajcn.2009.29094
Vallejo, Blümel, Arteaga, Aedo, Tapia et al., Gender Differences in the Prevalence of Vitamin D Deficiency in a Southern Latin American Country: A Pilot Study, Climacteric
Wacker, Holick, Vitamin D-Effects on Skeletal and Extraskeletal Health and the Need for Supplementation, Nutrients,
doi:10.3390/nu5010111
Warwick, Schulz, Günther, Gilsbach, Neme et al., A Hierarchical Regulatory Network Analysis of the Vitamin D Induced Transcriptome Reveals Novel Regulators and Complete VDR Dependency in Monocytes, Sci. Rep,
doi:10.1038/s41598-021-86032-5
Zhou, Bu, Sun, Ren, Qu et al., Evaluation of Serum IgM and IgG Antibodies in COVID-19 Patients by Enzyme Linked Immunosorbent Assay, J. Med. Virol,
doi:10.1002/jmv.26741
Zhumina, Li, Konovalova, Li, Ishmuratova et al., Plasma 25-Hydroxyvitamin D Levels and VDR Gene Expression in Peripheral Blood Mononuclear Cells of Leukemia Patients and Healthy Subjects in Central Kazakhstan, Nutrients,
doi:10.3390/nu12051229
{ 'indexed': {'date-parts': [[2023, 4, 7]], 'date-time': '2023-04-07T05:09:24Z', 'timestamp': 1680844164901},
'reference-count': 70,
'publisher': 'MDPI AG',
'issue': '7',
'license': [ { 'start': { 'date-parts': [[2023, 4, 6]],
'date-time': '2023-04-06T00:00:00Z',
'timestamp': 1680739200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the '
'vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated '
'with the body’s susceptibility to infectious diseases, including COVID-19. In this pilot '
'retrospective study, representatives of the Kazakh population (central Kazakhstan) were '
'divided into groups based on the test for IgM and IgG for coronavirus infection. We compared '
'the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL '
'± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 '
'ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within '
'the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time '
'PCR assay. Allele C predominated among the COVID-19-negative participants and significantly '
'reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI '
'0.02357–0.2798). There were no statistically significant differences in the frequencies of '
'the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was '
'associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ2 = '
'5.364; OR = 4.131; 95% CI 1.223–13.71). Comprehensive studies are required to determine '
'whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for '
'COVID-19 infection.</jats:p>',
'DOI': '10.3390/nu15071781',
'type': 'journal-article',
'created': {'date-parts': [[2023, 4, 6]], 'date-time': '2023-04-06T05:10:27Z', 'timestamp': 1680757827000},
'page': '1781',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Plasma 25-Hydroxyvitamin D Level and VDR Gene Single Nucleotide Polymorphism rs2228570 Influence '
'on COVID-19 Susceptibility among the Kazakh Ethnic Group—A Pilot Study',
'prefix': '10.3390',
'volume': '15',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-8863-6713',
'authenticated-orcid': False,
'given': 'Valeriya V.',
'family': 'Protas',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Botany, Karaganda Buketov University, Karaganda '
'100028, Kazakhstan'}]},
{ 'given': 'Gayane P.',
'family': 'Pogossyan',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Botany, Karaganda Buketov University, Karaganda '
'100028, Kazakhstan'}]},
{ 'given': 'Konstantin G.',
'family': 'Li',
'sequence': 'additional',
'affiliation': [ { 'name': 'Biotechnology and Eco-Monitoring Research Park, Karaganda '
'Buketov University, Karaganda 100028, Kazakhstan'}]},
{ 'given': 'Assel G.',
'family': 'Zhumina',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Botany, Karaganda Buketov University, Karaganda '
'100028, Kazakhstan'}]},
{ 'given': 'Anar K.',
'family': 'Bisseneva',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Botany, Karaganda Buketov University, Karaganda '
'100028, Kazakhstan'}]},
{ 'given': 'Dinara N.',
'family': 'Shaikina',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Biology, Non-Profit Limited Company “Manash '
'Kozybayev North Kazakhstan University”, Petropavlovsk 150000, '
'Kazakhstan'}]}],
'member': '1968',
'published-online': {'date-parts': [[2023, 4, 6]]},
'reference': [ { 'key': 'ref_1',
'doi-asserted-by': 'crossref',
'first-page': '328',
'DOI': '10.1016/j.bj.2020.04.007',
'article-title': 'COVID-19: The First Documented Coronavirus Pandemic in History',
'volume': '43',
'author': 'Liu',
'year': '2020',
'journal-title': 'Biomed. J.'},
{ 'key': 'ref_2',
'unstructured': '(2023, March 28). COVID—Coronavirus Statistics—Worldometer. Available '
'online: https://www.worldometers.info/coronavirus/.'},
{ 'key': 'ref_3',
'doi-asserted-by': 'crossref',
'first-page': '577',
'DOI': '10.1002/jmv.25757',
'article-title': 'COVID-19 Patients’ Clinical Characteristics, Discharge Rate, and '
'Fatality Rate of Meta-analysis',
'volume': '92',
'author': 'Li',
'year': '2020',
'journal-title': 'J. Med. Virol.'},
{ 'key': 'ref_4',
'doi-asserted-by': 'crossref',
'first-page': '111356',
'DOI': '10.1016/j.nut.2021.111356',
'article-title': 'The Possible Benefits of Vitamin D in COVID-19',
'volume': '91–92',
'author': 'Brito',
'year': '2021',
'journal-title': 'Nutrition'},
{ 'key': 'ref_5',
'doi-asserted-by': 'crossref',
'first-page': '102661',
'DOI': '10.1016/j.amsu.2021.102661',
'article-title': 'Vitamin D Deficiency and COVID-19: A Case-Control Study at a Tertiary '
'Care Hospital in India',
'volume': '68',
'author': 'Nimavat',
'year': '2021',
'journal-title': 'Ann. Med. Surg.'},
{ 'key': 'ref_6',
'doi-asserted-by': 'crossref',
'first-page': '143',
'DOI': '10.1016/j.gene.2004.05.014',
'article-title': 'Genetics and Biology of Vitamin D Receptor Polymorphisms',
'volume': '338',
'author': 'Uitterlinden',
'year': '2004',
'journal-title': 'Gene'},
{ 'key': 'ref_7',
'doi-asserted-by': 'crossref',
'first-page': '198235',
'DOI': '10.1016/j.virusres.2020.198235',
'article-title': 'Putative Roles of Vitamin D in Modulating Immune Response and '
'Immunopathology Associated with COVID-19',
'volume': '292',
'author': 'Kumar',
'year': '2021',
'journal-title': 'Virus Res.'},
{ 'key': 'ref_8',
'doi-asserted-by': 'crossref',
'first-page': '192',
'DOI': '10.1016/j.aimed.2020.07.011',
'article-title': 'The Effects of Vitamin D on Acute Viral Respiratory Infections: A Rapid '
'Review',
'volume': '7',
'author': 'Bradley',
'year': '2020',
'journal-title': 'Adv. Integr. Med.'},
{ 'key': 'ref_9',
'doi-asserted-by': 'crossref',
'first-page': '101509',
'DOI': '10.1016/j.genrep.2022.101509',
'article-title': 'Serum Levels of Vitamin D and Immune System Function in Patients with '
'COVID-19 Admitted to Intensive Care Unit',
'volume': '26',
'author': 'Mahmoodpoor',
'year': '2022',
'journal-title': 'Gene Rep.'},
{ 'key': 'ref_10',
'doi-asserted-by': 'crossref',
'first-page': '1373',
'DOI': '10.1016/j.jiph.2020.06.021',
'article-title': 'Role of Vitamin D in Preventing of COVID-19 Infection, Progression and '
'Severity',
'volume': '13',
'author': 'Ali',
'year': '2020',
'journal-title': 'J. Infect. Public Health'},
{ 'key': 'ref_11',
'doi-asserted-by': 'crossref',
'first-page': '97',
'DOI': '10.1016/j.afos.2020.07.003',
'article-title': 'Vitamin D in COVID-19: Dousing the Fire or Averting the Storm?—A '
'Perspective from the Asia-Pacific',
'volume': '6',
'author': 'Chandran',
'year': '2020',
'journal-title': 'Osteoporos. Sarcopenia'},
{ 'key': 'ref_12',
'doi-asserted-by': 'crossref',
'first-page': '111',
'DOI': '10.3390/nu5010111',
'article-title': 'Vitamin D—Effects on Skeletal and Extraskeletal Health and the Need for '
'Supplementation',
'volume': '5',
'author': 'Wacker',
'year': '2013',
'journal-title': 'Nutrients'},
{ 'key': 'ref_13',
'doi-asserted-by': 'crossref',
'first-page': '96',
'DOI': '10.1016/j.ijpp.2018.01.002',
'article-title': 'The Discovery and Synthesis of the Nutritional Factor Vitamin D',
'volume': '23',
'author': 'Jones',
'year': '2018',
'journal-title': 'Int. J. Paleopathol.'},
{ 'key': 'ref_14',
'doi-asserted-by': 'crossref',
'first-page': '757',
'DOI': '10.1016/j.dsx.2021.03.006',
'article-title': 'Impact of the Vitamin D Deficiency on COVID-19 Infection and Mortality '
'in Asian Countries',
'volume': '15',
'author': 'Jayawardena',
'year': '2021',
'journal-title': 'Diabetes Metab. Syndr. Clin. Res. Rev.'},
{ 'key': 'ref_15',
'doi-asserted-by': 'crossref',
'first-page': '103',
'DOI': '10.1016/j.mce.2010.02.013',
'article-title': 'Vitamin D and the Intracrinology of Innate Immunity',
'volume': '321',
'author': 'Hewison',
'year': '2010',
'journal-title': 'Mol. Cell. Endocrinol.'},
{ 'key': 'ref_16',
'doi-asserted-by': 'crossref',
'first-page': '10',
'DOI': '10.1016/j.nfs.2020.06.001',
'article-title': 'Vitamin D Deficiency and Co-Morbidities in COVID-19 Patients—A Fatal '
'Relationship?',
'volume': '20',
'author': 'Biesalski',
'year': '2020',
'journal-title': 'NFS J.'},
{ 'key': 'ref_17',
'doi-asserted-by': 'crossref',
'first-page': '105565',
'DOI': '10.1016/j.jsbmb.2019.105565',
'article-title': 'Vitamin D Deficiency in Kazakhstan: Cross-Sectional Study',
'volume': '199',
'author': 'Gromova',
'year': '2020',
'journal-title': 'J. Steroid Biochem. Mol. Biol.'},
{ 'key': 'ref_18',
'doi-asserted-by': 'crossref',
'unstructured': 'Bergman, P., Lindh, A.U., Björkhem-Bergman, L., and Lindh, J.D. (2013). '
'Vitamin D and Respiratory Tract Infections: A Systematic Review and '
'Meta-Analysis of Randomized Controlled Trials. PLoS ONE, 8.',
'DOI': '10.1371/journal.pone.0065835'},
{ 'key': 'ref_19',
'doi-asserted-by': 'crossref',
'first-page': '1255',
'DOI': '10.3945/ajcn.2009.29094',
'article-title': 'Randomized Trial of Vitamin D Supplementation to Prevent Seasonal '
'Influenza A in Schoolchildren',
'volume': '91',
'author': 'Urashima',
'year': '2010',
'journal-title': 'Am. J. Clin. Nutr.'},
{ 'key': 'ref_20',
'doi-asserted-by': 'crossref',
'first-page': '3693',
'DOI': '10.1111/febs.15495',
'article-title': 'Low Plasma 25(OH) Vitamin D Level Is Associated with Increased Risk of '
'COVID-19 Infection: An Israeli Population-based Study',
'volume': '287',
'author': 'Merzon',
'year': '2020',
'journal-title': 'FEBS J.'},
{ 'key': 'ref_21',
'doi-asserted-by': 'crossref',
'unstructured': 'Kaufman, H.W., Niles, J.K., Kroll, M.H., Bi, C., and Holick, M.F. '
'(2020). SARS-CoV-2 Positivity Rates Associated with Circulating '
'25-Hydroxyvitamin D Levels. PLoS ONE, 15.',
'DOI': '10.1371/journal.pone.0239252'},
{ 'key': 'ref_22',
'doi-asserted-by': 'crossref',
'first-page': '1609',
'DOI': '10.1007/s40520-020-01619-8',
'article-title': 'Revisiting the Role of Vitamin D Levels in the Prevention of COVID-19 '
'Infection and Mortality in European Countries Post Infections Peak',
'volume': '32',
'author': 'Singh',
'year': '2020',
'journal-title': 'Aging Clin. Exp. Res.'},
{ 'key': 'ref_23',
'doi-asserted-by': 'crossref',
'first-page': '107001',
'DOI': '10.1016/j.intimp.2020.107001',
'article-title': 'Lower Levels of Vitamin D Are Associated with SARS-CoV-2 Infection and '
'Mortality in the Indian Population: An Observational Study',
'volume': '88',
'author': 'Padhi',
'year': '2020',
'journal-title': 'Int. Immunopharmacol.'},
{ 'key': 'ref_24',
'doi-asserted-by': 'crossref',
'first-page': '111441',
'DOI': '10.1016/j.nut.2021.111441',
'article-title': 'A Critical Update on the Role of Mild and Serious Vitamin D Deficiency '
'Prevalence and the COVID-19 Epidemic in Europe',
'volume': '93',
'author': 'Bakaloudi',
'year': '2022',
'journal-title': 'Nutrition'},
{ 'key': 'ref_25',
'doi-asserted-by': 'crossref',
'first-page': '561',
'DOI': '10.1016/j.dsx.2020.04.050',
'article-title': 'Vitamin D Concentrations and COVID-19 Infection in UK Biobank',
'volume': '14',
'author': 'Hastie',
'year': '2020',
'journal-title': 'Diabetes Metab. Syndr. Clin. Res. Rev.'},
{ 'key': 'ref_26',
'doi-asserted-by': 'crossref',
'first-page': '319',
'DOI': '10.1016/j.chembiol.2013.12.016',
'article-title': 'Vitamin D Metabolism, Mechanism of Action, and Clinical Applications',
'volume': '21',
'author': 'Bikle',
'year': '2014',
'journal-title': 'Chem. Biol.'},
{ 'key': 'ref_27',
'doi-asserted-by': 'crossref',
'first-page': '547',
'DOI': '10.1016/j.ejcdt.2014.02.012',
'article-title': 'Association between Vitamin D Receptor Gene FokI Polymorphism and '
'Atopic Childhood Bronchial Asthma',
'volume': '63',
'author': 'Nabih',
'year': '2014',
'journal-title': 'Egypt. J. Chest Dis. Tuberc.'},
{ 'key': 'ref_28',
'doi-asserted-by': 'crossref',
'first-page': '6518',
'DOI': '10.1038/s41598-021-86032-5',
'article-title': 'A Hierarchical Regulatory Network Analysis of the Vitamin D Induced '
'Transcriptome Reveals Novel Regulators and Complete VDR Dependency in '
'Monocytes',
'volume': '11',
'author': 'Warwick',
'year': '2021',
'journal-title': 'Sci. Rep.'},
{ 'key': 'ref_29',
'doi-asserted-by': 'crossref',
'first-page': '255',
'DOI': '10.1016/j.ecl.2010.02.007',
'article-title': 'The Vitamin D Receptor: New Paradigms for the Regulation of Gene '
'Expression by 1,25-Dihydroxyvitamin D3',
'volume': '39',
'author': 'Pike',
'year': '2010',
'journal-title': 'Endocrinol. Metab. Clin. N. Am.'},
{ 'key': 'ref_30',
'first-page': 'e2159',
'article-title': 'Vitamin D and Covid-19: From Potential Therapeutic Effects to '
'Unanswered Questions',
'volume': '31',
'author': 'Marashi',
'year': '2021',
'journal-title': 'Rev. Med. Virol.'},
{ 'key': 'ref_31',
'doi-asserted-by': 'crossref',
'unstructured': 'Tuoresmäki, P., Väisänen, S., Neme, A., Heikkinen, S., and Carlberg, C. '
'(2014). Patterns of Genome-Wide VDR Locations. PLoS ONE, 9.',
'DOI': '10.1371/journal.pone.0096105'},
{ 'key': 'ref_32',
'doi-asserted-by': 'crossref',
'first-page': '127',
'DOI': '10.1016/j.steroids.2012.10.019',
'article-title': 'Vitamin D Receptor Signaling Mechanisms: Integrated Actions of a '
'Well-Defined Transcription Factor',
'volume': '78',
'author': 'Carlberg',
'year': '2013',
'journal-title': 'Steroids'},
{ 'key': 'ref_33',
'doi-asserted-by': 'crossref',
'first-page': '105098',
'DOI': '10.1016/j.meegid.2021.105098',
'article-title': 'Association of Vitamin D Receptor Gene Polymorphisms and '
'Clinical/Severe Outcomes of COVID-19 Patients',
'volume': '96',
'author': 'Abdollahzadeh',
'year': '2021',
'journal-title': 'Infect. Genet. Evol.'},
{ 'key': 'ref_34',
'unstructured': '(2023, March 28). rs2228570—SNP—NCBI. Available online: '
'https://www.ncbi.nlm.nih.gov/snp/?term=rs2228570.'},
{ 'key': 'ref_35',
'doi-asserted-by': 'crossref',
'first-page': '7',
'DOI': '10.1016/j.gene.2017.12.022',
'article-title': 'Association between Single Nucleotide Polymorphisms in TLR4, TLR2, '
'TLR9, VDR, NOS2 and CCL5 Genes with Acute Viral Bronchiolitis',
'volume': '645',
'author': 'Alvarez',
'year': '2018',
'journal-title': 'Gene'},
{ 'key': 'ref_36',
'doi-asserted-by': 'crossref',
'first-page': '59',
'DOI': '10.1016/j.micpath.2019.02.027',
'article-title': 'A Meta-Analysis on Associations between Vitamin D Receptor Genetic '
'Variants and Tuberculosis',
'volume': '130',
'author': 'Wang',
'year': '2019',
'journal-title': 'Microb. Pathog.'},
{ 'key': 'ref_37',
'doi-asserted-by': 'crossref',
'first-page': '70',
'DOI': '10.1016/j.ijtb.2018.04.005',
'article-title': 'Association between Vitamin D Receptor Gene Polymorphisms and Pulmonary '
'Tuberculosis in a Mexican Population',
'volume': '66',
'year': '2019',
'journal-title': 'Indian J. Tuberc.'},
{ 'key': 'ref_38',
'doi-asserted-by': 'crossref',
'first-page': '1194',
'DOI': '10.1016/j.humimm.2012.08.007',
'article-title': 'Association of Vitamin D Receptor Gene Polymorphisms with Clinical '
'Outcomes of Dengue Virus Infection',
'volume': '73',
'author': 'Alagarasu',
'year': '2012',
'journal-title': 'Hum. Immunol.'},
{ 'key': 'ref_39',
'doi-asserted-by': 'crossref',
'first-page': '1834',
'DOI': '10.1002/jmv.22179',
'article-title': 'Confirmation of an Association between Single Nucleotide Polymorphisms '
'in the VDR Gene with Respiratory Syncytial Virus Related Disease in '
'South African Children',
'volume': '83',
'author': 'Kresfelder',
'year': '2011',
'journal-title': 'J. Med. Virol.'},
{ 'key': 'ref_40',
'doi-asserted-by': 'crossref',
'first-page': '243',
'DOI': '10.1111/iji.12585',
'article-title': 'VDR Gene Polymorphisms Are Associated with the Increased Susceptibility '
'to COVID-19 among Iranian Population: A Case-control Study',
'volume': '49',
'author': 'Jafarpoor',
'year': '2022',
'journal-title': 'Int. J. Immunogenet.'},
{ 'key': 'ref_41',
'doi-asserted-by': 'crossref',
'first-page': '689419',
'DOI': '10.3389/fnut.2021.689419',
'article-title': 'Association of Vitamin D, Zinc and Selenium Related Genetic Variants '
'With COVID-19 Disease Severity',
'volume': '8',
'author': 'Kotur',
'year': '2021',
'journal-title': 'Front. Nutr.'},
{ 'key': 'ref_42',
'doi-asserted-by': 'crossref',
'first-page': '819',
'DOI': '10.1111/cen.14664',
'article-title': 'Effects of Vitamin D Receptor Gene Polymorphisms on the Prognosis of '
'COVID-19',
'volume': '96',
'author': 'Apaydin',
'year': '2022',
'journal-title': 'Clin. Endocrinol.'},
{ 'key': 'ref_43',
'doi-asserted-by': 'crossref',
'first-page': '21',
'DOI': '10.1016/j.ajic.2020.07.011',
'article-title': 'Systematic Review with Meta-Analysis of the Accuracy of Diagnostic '
'Tests for COVID-19',
'volume': '49',
'author': 'Fachi',
'year': '2021',
'journal-title': 'Am. J. Infect. Control'},
{ 'key': 'ref_44',
'doi-asserted-by': 'crossref',
'first-page': '565',
'DOI': '10.1016/S1473-3099(20)30196-1',
'article-title': 'Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva '
'Samples and Serum Antibody Responses during Infection by SARS-CoV-2: An '
'Observational Cohort Study',
'volume': '20',
'author': 'To',
'year': '2020',
'journal-title': 'Lancet Infect. Dis.'},
{ 'key': 'ref_45',
'doi-asserted-by': 'crossref',
'first-page': '2249',
'DOI': '10.1001/jama.2020.8259',
'article-title': 'Interpreting Diagnostic Tests for SARS-CoV-2',
'volume': '323',
'author': 'Sethuraman',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'ref_46',
'doi-asserted-by': 'crossref',
'first-page': '2857',
'DOI': '10.1002/jmv.26741',
'article-title': 'Evaluation of Serum IgM and IgG Antibodies in COVID-19 Patients by '
'Enzyme Linked Immunosorbent Assay',
'volume': '93',
'author': 'Zhou',
'year': '2021',
'journal-title': 'J. Med. Virol.'},
{ 'key': 'ref_47',
'doi-asserted-by': 'crossref',
'first-page': '57',
'DOI': '10.1016/j.ijid.2021.04.078',
'article-title': 'Dynamic Changes and Prevalence of SARS-CoV-2 IgG/IgM Antibodies: '
'Analysis of Multiple Factors',
'volume': '108',
'author': 'Luo',
'year': '2021',
'journal-title': 'Int. J. Infect. Dis.'},
{ 'key': 'ref_48',
'doi-asserted-by': 'crossref',
'first-page': '11',
'DOI': '10.3904/kjim.2020.325',
'article-title': 'Dynamics of Viral Load and Anti-SARS-CoV-2 Antibodies in Patients with '
'Positive RT-PCR Results after Recovery from COVID-19',
'volume': '36',
'author': 'Song',
'year': '2021',
'journal-title': 'Korean J. Intern. Med.'},
{ 'key': 'ref_49',
'first-page': 'e5721',
'article-title': 'The Association between Body Mass Index and Vitamin D Supplement Use '
'among Adults in the United States',
'volume': '11',
'author': 'Orces',
'year': '2019',
'journal-title': 'Cureus'},
{ 'key': 'ref_50',
'doi-asserted-by': 'crossref',
'first-page': '52',
'DOI': '10.14341/2071-8713-4886',
'article-title': 'The Dependency of Vitamin D Status on Body Mass Index, Gender, Age and '
'Season',
'volume': '6',
'author': 'Lagunova',
'year': '2009',
'journal-title': 'Obes. Metab.'},
{ 'key': 'ref_51',
'doi-asserted-by': 'crossref',
'unstructured': 'Muscogiuri, G., Barrea, L., Somma, C.D., Laudisio, D., Salzano, C., '
'Pugliese, G., de Alteriis, G., Colao, A., and Savastano, S. (2019). Sex '
'Differences of Vitamin D Status across BMI Classes: An Observational '
'Prospective Cohort Study. Nutrients, 11.',
'DOI': '10.3390/nu11123034'},
{ 'key': 'ref_52',
'doi-asserted-by': 'crossref',
'first-page': '100041',
'DOI': '10.1016/j.medidd.2020.100041',
'article-title': 'Does Vitamin D Status Impact Mortality from SARS-CoV-2 Infection?',
'volume': '6',
'author': 'Marik',
'year': '2020',
'journal-title': 'Med. Drug Discov.'},
{ 'key': 'ref_53',
'doi-asserted-by': 'crossref',
'first-page': '372',
'DOI': '10.1016/j.clnesp.2021.05.011',
'article-title': 'Impact of Vitamin D Deficiency on COVID-19',
'volume': '44',
'author': 'Sooriyaarachchi',
'year': '2021',
'journal-title': 'Clin. Nutr. ESPEN'},
{ 'key': 'ref_54',
'doi-asserted-by': 'crossref',
'unstructured': 'D’Avolio, A., Avataneo, V., Manca, A., Cusato, J., De Nicolò, A., '
'Lucchini, R., Keller, F., and Cantù, M. (2020). 25-Hydroxyvitamin D '
'Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. '
'Nutrients, 12.',
'DOI': '10.3390/nu12051359'},
{ 'key': 'ref_55',
'doi-asserted-by': 'crossref',
'unstructured': 'Gallelli, L., Mannino, G.C., Luciani, F., de Sire, A., Mancuso, E., '
'Gangemi, P., Cosco, L., Monea, G., Averta, C., and Minchella, P. (2021). '
'Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the '
'Differences among Acute, Healed, and Negative COVID-19 Patients? A '
'Multicenter Real-Practice Study. Nutrients, 13.',
'DOI': '10.3390/nu13113932'},
{ 'key': 'ref_56',
'doi-asserted-by': 'crossref',
'first-page': '1053',
'DOI': '10.1007/s11739-021-02902-w',
'article-title': 'Vitamin D Deficiency Is Associated with Higher Risks for SARS-CoV-2 '
'Infection and COVID-19 Severity: A Retrospective Case–Control Study',
'volume': '17',
'author': 'Israel',
'year': '2022',
'journal-title': 'Intern. Emerg. Med.'},
{ 'key': 'ref_57',
'doi-asserted-by': 'crossref',
'first-page': '106',
'DOI': '10.1002/2211-5463.13309',
'article-title': 'Seasonal UV Exposure and Vitamin D: Association with the Dynamics of '
'COVID-19 Transmission in Europe',
'volume': '12',
'author': 'Mukherjee',
'year': '2021',
'journal-title': 'FEBS Open Bio.'},
{ 'key': 'ref_58',
'doi-asserted-by': 'crossref',
'first-page': '2115',
'DOI': '10.1017/S0007114522000149',
'article-title': 'Sex Differences in Vitamin D Metabolism, Serum Levels and Action',
'volume': '128',
'author': 'Wierzbicka',
'year': '2022',
'journal-title': 'Br. J. Nutr.'},
{ 'key': 'ref_59',
'doi-asserted-by': 'crossref',
'first-page': '410',
'DOI': '10.1080/13697137.2020.1752171',
'article-title': 'Gender Differences in the Prevalence of Vitamin D Deficiency in a '
'Southern Latin American Country: A Pilot Study',
'volume': '23',
'author': 'Vallejo',
'year': '2020',
'journal-title': 'Climacteric'},
{ 'key': 'ref_60',
'doi-asserted-by': 'crossref',
'first-page': '49',
'DOI': '10.1007/s11657-018-0461-5',
'article-title': 'Age and Gender Differences in the Prevalence and Correlates of Vitamin '
'D Deficiency',
'volume': '13',
'author': 'AlQuaiz',
'year': '2018',
'journal-title': 'Arch. Osteoporos.'},
{ 'key': 'ref_61',
'doi-asserted-by': 'crossref',
'unstructured': 'Zhumina, A.G., Li, K., Konovalova, A.A., Li, Y.A., Ishmuratova, M.Y., '
'Pogossyan, G.P., and Danilenko, M. (2020). Plasma 25-Hydroxyvitamin D '
'Levels and VDR Gene Expression in Peripheral Blood Mononuclear Cells of '
'Leukemia Patients and Healthy Subjects in Central Kazakhstan. Nutrients, '
'12.',
'DOI': '10.3390/nu12051229'},
{ 'key': 'ref_62',
'doi-asserted-by': 'crossref',
'first-page': '106',
'DOI': '10.1007/s00223-012-9660-z',
'article-title': 'Genetic Regulation of Vitamin D Levels',
'volume': '92',
'author': 'Dastani',
'year': '2013',
'journal-title': 'Calcif. Tissue Int.'},
{ 'key': 'ref_63',
'doi-asserted-by': 'crossref',
'first-page': '81',
'DOI': '10.1159/000514338',
'article-title': 'Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin '
'D Levels in a Greek Rural Population (Velestino Study)',
'volume': '14',
'author': 'Divanoglou',
'year': '2021',
'journal-title': 'Lifestyle Genom.'},
{ 'key': 'ref_64',
'doi-asserted-by': 'crossref',
'first-page': '815',
'DOI': '10.1111/j.1365-2133.2012.11132.x',
'article-title': 'The Association of Vitamin D Receptor Gene Polymorphisms and Serum '
'25-Hydroxyvitamin D Levels with Generalized Vitiligo: Association of '
'VDR Polymorphisms and Vitiligo Risk',
'volume': '167',
'author': 'Li',
'year': '2012',
'journal-title': 'Br. J. Dermatol.'},
{ 'key': 'ref_65',
'first-page': '77',
'article-title': 'The study of the association between rs2228570 polymorphism of VDR gene '
'and vitamin D blood serum concentration in the inhabitants of the '
'Russian Arctic',
'volume': '86',
'author': 'Baturin',
'year': '2017',
'journal-title': 'Vopr. Pitan.'},
{ 'key': 'ref_66',
'doi-asserted-by': 'crossref',
'first-page': '100945',
'DOI': '10.1016/j.mgene.2021.100945',
'article-title': 'Relationship between Vitamin D Receptor Gene FokI Polymorphism and '
'25-Hydroxyvitamin D Levels in Apparently Healthy Syrians',
'volume': '29',
'author': 'Mohammad',
'year': '2021',
'journal-title': 'Meta Gene'},
{ 'key': 'ref_67',
'doi-asserted-by': 'crossref',
'first-page': '108',
'DOI': '10.4103/0971-6866.60186',
'article-title': 'Frequency of FokI and TaqI Polymorphism of Vitamin D Receptor Gene in '
'Indian Population and Its Association with 25-Hydroxyvitamin D Levels',
'volume': '15',
'author': 'Das',
'year': '2009',
'journal-title': 'Indian J. Hum. Genet.'},
{ 'key': 'ref_68',
'doi-asserted-by': 'crossref',
'first-page': '131',
'DOI': '10.4103/idoj.IDOJ_97_18',
'article-title': 'Association of Vitamin D Receptor Gene Polymorphisms and Serum '
'25-Hydroxy Vitamin D Levels in Vitiligo—A Case-Control Study',
'volume': '10',
'author': 'Hassan',
'year': '2019',
'journal-title': 'Indian Dermatol. Online J.'},
{ 'key': 'ref_69',
'doi-asserted-by': 'crossref',
'first-page': '384',
'DOI': '10.1016/j.gene.2018.08.017',
'article-title': 'Vitamin D Receptor Polymorphisms and Risk of Enveloped Virus Infection: '
'A Meta-Analysis',
'volume': '678',
'author': 'Laplana',
'year': '2018',
'journal-title': 'Gene'},
{ 'key': 'ref_70',
'doi-asserted-by': 'crossref',
'first-page': '2089',
'DOI': '10.1007/s00705-021-05070-6',
'article-title': 'Human Gene Polymorphisms and Their Possible Impact on the Clinical '
'Outcome of SARS-CoV-2 Infection',
'volume': '166',
'author': 'Hashemi',
'year': '2021',
'journal-title': 'Arch. Virol.'}],
'container-title': 'Nutrients',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/15/7/1781/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 4, 6]],
'date-time': '2023-04-06T05:59:22Z',
'timestamp': 1680760762000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/15/7/1781'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 4, 6]]},
'references-count': 70,
'journal-issue': {'issue': '7', 'published-online': {'date-parts': [[2023, 4]]}},
'alternative-id': ['nu15071781'],
'URL': 'http://dx.doi.org/10.3390/nu15071781',
'relation': {},
'ISSN': ['2072-6643'],
'subject': ['Food Science', 'Nutrition and Dietetics'],
'container-title-short': 'Nutrients',
'published': {'date-parts': [[2023, 4, 6]]}}