Investigation of the Relationship between Vitamin D Deficiency and Vitamin D-Binding Protein Polymorphisms in Severe COVID-19 Patients
Lutfiye Karcıoğlu Batur, Mehmet Dokur, Suna Koç, Mehmet Karabay, Zeyneb Nur Akcay, Ezgi Gunger, Nezih Hekim
Diagnostics, doi:10.3390/diagnostics14171941
This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age-and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms rs5488 and rs7041 were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) (p = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous rs7041 (60.7%) and wild-type rs4588 (58.9%) genotypes. The distribution of rs7041 SNP varied significantly among groups (p = 0.0301), while rs4588 SNP distribution did not (p = 0.424). Heterozygous rs4588 patients had significantly lower VDBP levels (p = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type rs4588 (p = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly rs7041 and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflict of interest.
References
Al-Daghri, Mohammed, Bukhari, Rikli, Abdi et al., Efficacy of vitamin D supplementation according to vitamin D-binding protein polymorphisms, Nutrition,
doi:10.1016/j.nut.2019.02.003
Alharazy, Naseer, Alissa, Robertson, Lanham-New et al., Association of SNPs in GC and CYP2R1 with total and directly measured free 25-hydroxyvitamin D in multi-ethnic postmenopausal women in Saudi Arabia, Saudi J. Biol. Sci,
doi:10.1016/j.sjbs.2021.04.071
Aloia, Mikhail, Dhaliwal, Shieh, Usera et al., Free 25(OH)D and the Vitamin D Paradox in African Americans, J. Clin. Endocrinol. Metab,
doi:10.1210/JC.2015-2066
Apaydin, Polat, Dincer Yazan, Ilgin, Elbasan et al., Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19, Clin. Endocrinol,
doi:10.1111/cen.14664
Arnaud, Constans, Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP), Hum. Genet,
doi:10.1007/BF00219689
Barrea, Verde, Grant, Frias-Toral, Sarno et al., Vitamin D: A Role Also in Long COVID-19?, Nutrients,
doi:10.3390/nu14081625
Batur, Koç, Association between Vitamin D Status and Secondary Infections in Patients with Severe COVID-19 Admitted in the Intensive Care Unit of a Tertiary-Level Hospital in Turkey, Diagnostics,
doi:10.3390/diagnostics13010059
Bikle, Schwartz, Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions, Front. Endocrinol,
doi:10.3389/fendo.2019.00317
Charoenngam, Jaroenlapnopparat, Mettler, Grover, Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence, Biomedicines,
doi:10.3390/biomedicines11020400
Delanghe, De Buyzere, Speeckaert, Genetic polymorphisms in the host and COVID-19 infection
Dissanayake, De Silva, Sumanatilleke, De Silva, Gamage et al., Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis, J. Clin. Endocrinol. Metab,
doi:10.1210/clinem/dgab892
Erasmus, Maepa, Machingura, Davids, Raghubeer et al., Vitamin D-Binding Proteins, and VDR Polymorphisms in Individuals with Hyperglycaemia, Nutrients,
doi:10.3390/nu14153147
Faul, Erdfelder, Buchner, Lang, Statistical power analyses using G* Power 3.1: Tests for correlation and regression analyses, Behav. Res. Methods,
doi:10.3758/BRM.41.4.1149
Freitas, Calhau, Antunes, Araújo, Bandeira et al., Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity, Sci. Rep,
doi:10.1038/s41598-021-99952-z
Gibbons, Norton, Mccullough, Meltzer, Lavigne et al., Association between vitamin D supplementation and COVID-19 infection and mortality, Sci. Rep
Hafez, Saleh, Arya, Alzouhbi, Fdl Alla et al., Vitamin D Status in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients, Front. Med,
doi:10.3389/fmed.2022.843737
Jiang, Deng, Zhang, Cai, Cheung et al., Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19), J. Gen. Intern. Med,
doi:10.1007/s11606-020-05762-w
Kahar, Yusrawati, Jamsari, Maskoen, Aribowo et al., Association between Polymorphism Locus rs7041 and rs4588 in VDBP Gene and Vitamin D Status with Mortality in Sepsis Patient, J. Hunan Univ. Nat. Sci,
doi:10.55463/issn.1674-2974.50.2.15
Karcioglu Batur, Hekim, The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate, J. Med. Virol,
doi:10.1002/jmv.26409
Kaya, Pamukçu, Yakar, The role of vitamin D deficiency on COVID-19: A systematic review and meta-analysis of observational studies, Epidemiol. Health,
doi:10.4178/epih.e2021074
Laird, Rhodes, Kenny, Vitamin D and Inflammation: Potential Implications for Severity of COVID-19, Ir. Med. J
Little, Higgins, Ioannidis, Moher, Gagnon et al., STrengthening the REporting of Genetic Association studies (STREGA)-An extension of the STROBE statement, Eur. J. Clin. Investig,
doi:10.1111/j.1365-2362.2009.02125.x
Mariani, Giménez, Bergam, Tajer, Antonietti et al., Association Between Vitamin D Deficiency and COVID-19 Incidence, Complications, and Mortality in 46 Countries: An Ecological Study, Health Secur,
doi:10.1089/hs.2020.0137
Mcgrath, Saha, Burne, Eyles, A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2010.03.073
Mondul, Weinstein, Virtamo, Albanes, Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer, Br. J. Cancer,
doi:10.1038/bjc.2012.417
Pereira, Dantas Damascena, Galvão Azevedo, De Almeida Oliveira, Da Mota Santana, Vitamin D deficiency aggravates COVID-19: Systematic review and meta-analysis, Crit. Rev. Food Sci. Nutr,
doi:10.1080/10408398.2020.1841090
Ross, Manson, Abrams, Aloia, Brannon et al., The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2010-2704
Rozmus, Ciesielska, Płomi Ński, Grzybowski, Fiedorowicz et al., Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases, Int. J. Mol. Sci,
doi:10.3390/ijms21217822
Rozmus, Płomi Ński, Augustyn, Cieśli ńska, A. rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) and the Risk of Diseases, Int. J. Mol. Sci,
doi:10.3390/ijms23020933
Speeckaert, De Buyzere, Delanghe, Vitamin D binding protein polymorphism and COVID-19, J. Med. Virol,
doi:10.1002/jmv.26508
Thacher, Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19, Nutrients,
doi:10.3390/nu14030464
Wang, Joshi, Leopold, Jackson, Christensen et al., Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis, Clin. Endocrinol,
doi:10.1111/cen.14540
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'reference': [ { 'key': 'ref_1',
'unstructured': '(2024, June 12). WHO Coronavirus (COVID-19) Dashboard. Available online: '
'https://covid19.who.int.'},
{ 'key': 'ref_2',
'doi-asserted-by': 'crossref',
'first-page': '1545',
'DOI': '10.1007/s11606-020-05762-w',
'article-title': 'Review of the Clinical Characteristics of Coronavirus Disease 2019 '
'(COVID-19)',
'volume': '35',
'author': 'Jiang',
'year': '2020',
'journal-title': 'J. Gen. Intern. Med.'},
{ 'key': 'ref_3',
'doi-asserted-by': 'crossref',
'first-page': '470',
'DOI': '10.1016/S0140-6736(20)30185-9',
'article-title': 'A novel coronavirus outbreak of global health concern',
'volume': '395',
'author': 'Wang',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': 'ref_4',
'doi-asserted-by': 'crossref',
'first-page': '365',
'DOI': '10.1080/10408363.2020.1783198',
'article-title': 'The COVID-19 pandemic',
'volume': '57',
'author': 'Ciotti',
'year': '2020',
'journal-title': 'Crit. Rev. Clin. Lab. Sci.'},
{ 'key': 'ref_5',
'doi-asserted-by': 'crossref',
'unstructured': 'Bikle, D.D., and Schwartz, J. (2019). Vitamin D Binding Protein, Total '
'and Free Vitamin D Levels in Different Physiological and '
'Pathophysiological Conditions. Front. Endocrinol., 10.',
'DOI': '10.3389/fendo.2019.00317'},
{ 'key': 'ref_6',
'doi-asserted-by': 'crossref',
'unstructured': 'Hafez, W., Saleh, H., Arya, A., Alzouhbi, M., Fdl Alla, O., Lal, K., '
'Kishk, S., Ali, S., Raghu, S., and Elgaili, W. (2022). Vitamin D Status '
'in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients. '
'Front. Med., 9.',
'DOI': '10.3389/fmed.2022.843737'},
{ 'key': 'ref_7',
'doi-asserted-by': 'crossref',
'unstructured': 'Rozmus, D., Płomiński, J., Augustyn, K., and Cieślińska, A. (2022). '
'rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) '
'and the Risk of Diseases. Int. J. Mol. Sci., 23.',
'DOI': '10.3390/ijms23020933'},
{ 'key': 'ref_8',
'first-page': '148',
'article-title': 'Efficacy of vitamin D supplementation according to vitamin D-binding '
'protein polymorphisms',
'volume': '63–64',
'author': 'Mohammed',
'year': '2019',
'journal-title': 'Nutrition'},
{ 'key': 'ref_9',
'doi-asserted-by': 'crossref',
'first-page': '4626',
'DOI': '10.1016/j.sjbs.2021.04.071',
'article-title': 'Association of SNPs in GC and CYP2R1 with total and directly measured '
'free 25-hydroxyvitamin D in multi-ethnic postmenopausal women in Saudi '
'Arabia',
'volume': '28',
'author': 'Alharazy',
'year': '2021',
'journal-title': 'Saudi J. Biol. Sci.'},
{ 'key': 'ref_10',
'doi-asserted-by': 'crossref',
'unstructured': 'Rozmus, D., Ciesielska, A., Płomiński, J., Grzybowski, R., Fiedorowicz, '
'E., Kordulewska, N., Savelkoul, H., Kostyra, E., and Cieślińska, A. '
'(2020). Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms—The '
'Risk of Malignant Tumors and Other Diseases. Int. J. Mol. Sci., 21.',
'DOI': '10.3390/ijms21217822'},
{ 'key': 'ref_11',
'doi-asserted-by': 'crossref',
'first-page': '471',
'DOI': '10.1016/j.jsbmb.2010.03.073',
'article-title': 'A systematic review of the association between common single nucleotide '
'polymorphisms and 25-hydroxyvitamin D concentrations',
'volume': '121',
'author': 'McGrath',
'year': '2010',
'journal-title': 'J. Steroid Biochem. Mol. Biol.'},
{ 'key': 'ref_12',
'doi-asserted-by': 'crossref',
'first-page': '1409',
'DOI': '10.1002/jmv.26409',
'article-title': 'The role of DBP gene polymorphisms in the prevalence of new coronavirus '
'disease 2019 infection and mortality rate',
'volume': '93',
'author': 'Hekim',
'year': '2021',
'journal-title': 'J. Med. Virol.'},
{ 'key': 'ref_13',
'doi-asserted-by': 'crossref',
'unstructured': 'Thacher, T.D. (2022). Evaluating the Evidence in Clinical Studies of '
'Vitamin D in COVID-19. Nutrients, 14.',
'DOI': '10.3390/nu14030464'},
{ 'key': 'ref_14',
'doi-asserted-by': 'crossref',
'unstructured': 'Barrea, L., Verde, L., Grant, W.B., Frias-Toral, E., Sarno, G., Vetrani, '
'C., Ceriani, F., Garcia-Velasquez, E., Contreras-Briceño, J., and '
'Savastano, S. (2022). Vitamin D: A Role Also in Long COVID-19?. '
'Nutrients, 14.',
'DOI': '10.3390/nu14081625'},
{ 'key': 'ref_15',
'doi-asserted-by': 'crossref',
'unstructured': 'Batur, L.K., and Koç, S. (2022). Association between Vitamin D Status '
'and Secondary Infections in Patients with Severe COVID-19 Admitted in '
'the Intensive Care Unit of a Tertiary-Level Hospital in Turkey. '
'Diagnostics, 13.',
'DOI': '10.3390/diagnostics13010059'},
{ 'key': 'ref_16',
'doi-asserted-by': 'crossref',
'first-page': '302',
'DOI': '10.1089/hs.2020.0137',
'article-title': 'Association Between Vitamin D Deficiency and COVID-19 Incidence, '
'Complications, and Mortality in 46 Countries: An Ecological Study',
'volume': '19',
'author': 'Mariani',
'year': '2021',
'journal-title': 'Health Secur.'},
{ 'key': 'ref_17',
'first-page': '81',
'article-title': 'Vitamin D and Inflammation: Potential Implications for Severity of '
'COVID-19',
'volume': '113',
'author': 'Laird',
'year': '2020',
'journal-title': 'Ir. Med. J.'},
{ 'key': 'ref_18',
'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': '1',
'author': 'Ali',
'year': '2020',
'journal-title': 'J. Infect. Public Health'},
{ 'key': 'ref_19',
'doi-asserted-by': 'crossref',
'first-page': '247',
'DOI': '10.1111/j.1365-2362.2009.02125.x',
'article-title': 'STrengthening the REporting of Genetic Association studies (STREGA)—An '
'extension of the STROBE statement',
'volume': '39',
'author': 'Little',
'year': '2009',
'journal-title': 'Eur. J. Clin. Investig.'},
{ 'key': 'ref_20',
'doi-asserted-by': 'crossref',
'first-page': '53',
'DOI': '10.1210/jc.2010-2704',
'article-title': 'The 2011 report on dietary reference intakes for calcium and vitamin D '
'from the Institute of Medicine: What clinicians need to know',
'volume': '96',
'author': 'Ross',
'year': '2011',
'journal-title': 'J. Clin. Endocrinol. Metab.'},
{ 'key': 'ref_21',
'doi-asserted-by': 'crossref',
'first-page': '3356',
'DOI': '10.1210/JC.2015-2066',
'article-title': 'Free 25(OH)D and the Vitamin D Paradox in African Americans',
'volume': '100',
'author': 'Aloia',
'year': '2015',
'journal-title': 'J. Clin. Endocrinol. Metab.'},
{ 'key': 'ref_22',
'doi-asserted-by': 'crossref',
'first-page': '1589',
'DOI': '10.1038/bjc.2012.417',
'article-title': 'Influence of vitamin D binding protein on the association between '
'circulating vitamin D and risk of bladder cancer',
'volume': '107',
'author': 'Mondul',
'year': '2012',
'journal-title': 'Br. J. Cancer'},
{ 'key': 'ref_23',
'doi-asserted-by': 'crossref',
'first-page': '1149',
'DOI': '10.3758/BRM.41.4.1149',
'article-title': 'Statistical power analyses using G* Power 3.1: Tests for correlation '
'and regression analyses',
'volume': '41',
'author': 'Faul',
'year': '2009',
'journal-title': 'Behav. Res. Methods'},
{ 'key': 'ref_24',
'doi-asserted-by': 'crossref',
'first-page': '183',
'DOI': '10.1007/BF00219689',
'article-title': 'Affinity differences for vitamin D metabolites associated with the '
'genetic isoforms of the human serum carrier protein (DBP)',
'volume': '92',
'author': 'Arnaud',
'year': '1993',
'journal-title': 'Hum. Genet.'},
{ 'key': 'ref_25',
'doi-asserted-by': 'crossref',
'first-page': '281',
'DOI': '10.1111/cen.14540',
'article-title': 'Association of vitamin D deficiency with COVID-19 infection severity: '
'Systematic review and meta-analysis',
'volume': '96',
'author': 'Wang',
'year': '2022',
'journal-title': 'Clin. Endocrinol.'},
{ 'key': 'ref_26',
'doi-asserted-by': 'crossref',
'first-page': '1308',
'DOI': '10.1080/10408398.2020.1841090',
'article-title': 'Vitamin D deficiency aggravates COVID-19: Systematic review and '
'meta-analysis',
'volume': '62',
'author': 'Pereira',
'year': '2022',
'journal-title': 'Crit. Rev. Food Sci. Nutr.'},
{ 'key': 'ref_27',
'doi-asserted-by': 'crossref',
'first-page': '1484',
'DOI': '10.1210/clinem/dgab892',
'article-title': 'Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic '
'Review and Meta-analysis',
'volume': '107',
'author': 'Dissanayake',
'year': '2022',
'journal-title': 'J. Clin. Endocrinol. Metab.'},
{ 'key': 'ref_28',
'doi-asserted-by': 'crossref',
'first-page': 'e2021074',
'DOI': '10.4178/epih.e2021074',
'article-title': 'The role of vitamin D deficiency on COVID-19: A systematic review and '
'meta-analysis of observational studies',
'volume': '43',
'author': 'Kaya',
'year': '2021',
'journal-title': 'Epidemiol. Health'},
{ 'key': 'ref_29',
'doi-asserted-by': 'crossref',
'unstructured': 'Gibbons, J.B., Norton, E.C., McCullough, J.S., Meltzer, D.O., Lavigne, '
'J., Fiedler, V.C., and Gibbons, R.D. (2022). Association between vitamin '
'D supplementation and COVID-19 infection and mortality. Sci. Rep., 12.',
'DOI': '10.1038/s41598-022-24053-4'},
{ 'key': 'ref_30',
'doi-asserted-by': 'crossref',
'unstructured': 'Wöbke, T.K., Sorg, B.L., and Steinhilber, D. (2014). Vitamin D in '
'inflammatory diseases. Front. Physiol., 5.',
'DOI': '10.3389/fphys.2014.00244'},
{ 'key': 'ref_31',
'doi-asserted-by': 'crossref',
'first-page': '78',
'DOI': '10.1016/j.jaut.2017.07.007',
'article-title': 'Modulation of inflammatory and immune responses by Vitamin D',
'volume': '85',
'author': 'Colotta',
'year': '2017',
'journal-title': 'J. Autoimmun.'},
{ 'key': 'ref_32',
'doi-asserted-by': 'crossref',
'unstructured': 'Delanghe, J.R., De Buyzere, M.L., and Speeckaert, M.M. (2021). Genetic '
'polymorphisms in the host and COVID-19 infection. Coronavirus '
'Disease-COVID-19 2021 May 11, Springer International Publishing.',
'DOI': '10.1007/978-3-030-63761-3_7'},
{ 'key': 'ref_33',
'first-page': '150',
'article-title': 'Association between Polymorphism Locus rs7041 and rs4588 in VDBP Gene '
'and Vitamin D Status with Mortality in Sepsis Patient',
'volume': '50',
'author': 'Kahar',
'year': '2023',
'journal-title': 'J. Hunan Univ. Nat. Sci.'},
{ 'key': 'ref_34',
'doi-asserted-by': 'crossref',
'unstructured': 'Erasmus, R., Maepa, S., Machingura, I., Davids, S., Raghubeer, S., and '
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'author': 'Apaydin',
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'journal-title': 'Clin. Endocrinol.'},
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'article-title': 'Vitamin D binding protein polymorphism and COVID-19',
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'author': 'Speeckaert',
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'journal-title': 'J. Med. Virol.'},
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'Barreira, S., Bazenga, F., Braz, S., Caldeira, D., and Santos, S.C.R. '
'(2021). Vitamin D-related polymorphisms and vitamin D levels as risk '
'biomarkers of COVID-19 disease severity. Sci. Rep., 11.',
'DOI': '10.1038/s41598-021-99952-z'},
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'(2023). Genetic Variations of the Vitamin D Metabolic Pathway and '
'COVID-19 Susceptibility and Severity: Current Understanding and Existing '
'Evidence. Biomedicines, 11.',
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