Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents
Fatme Al-Anouti, Mira Mousa, Spyridon N Karras, William B Grant, Zainab Alhalwachi, Laila Abdel-Wareth, Maimunah Uddin, Nawal Alkaabi, Guan K Tay, Bassam Mahboub, Habiba Alsafar
Nutrients, doi:10.3390/nu13113680
Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.
References
Ahn, Yu, Stolzenberg-Solomon, Simon, Mccullough et al., Genome-wide association study of circulating vitamin D levels, Hum. Mol. Genet,
doi:10.1093/hmg/ddq155Al Anouti, Chehadeh, Osman, Elghazali, Al Safar, Investigating the association of vitamin D metabolism genes CYP2R1, CYP24A1 and CYP27B1 with vitamin D status in young adult Emiratis, J. Food Nutr. Res
Alsafar, Grant, Hijazi, Uddin, Alkaabi et al., COVID-19 disease severity and death in relation to vitamin D status among SARS-CoV-2-positive UAE residents, Nutrients,
doi:10.3390/nu13051714Castillo, Costa, Barrios, Díaz, 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, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105751Charoenngam, Shirvani, Reddy, Vodopivec, Apovian et al., Association of Vitamin D Status with Hospital Morbidity and Mortality in adult hospitalized patients with COVID-19, Endocr. Pract,
doi:10.1016/j.eprac.2021.02.013Chehadeh, Osman, Nazar, Jerman, Alghafri et al., Implication of genetic variants in overweight and obesity susceptibility among the young Arab population of the United Arab Emirates, Gene,
doi:10.1016/j.gene.2020.144509De Lucena, Da Silva Santos, De Lima, De Albuquerque Borborema, De Azevêdo et al., Mechanism of inflammatory response in associated comorbidities in COVID-19, Diabetes Metab. Syndr. Clin. Res. Rev
Di Maria, Latini, Borgiani, Novelli, Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): Rapid systematic review and field synopsis, Hum. Genom,
doi:10.1186/s40246-020-00280-6Elkum, Alkayal, Noronha, Ali, Melhem et al., Vitamin D insufficiency in Arabs and South Asians positively associates with polymorphisms in GC and CYP2R1 genes, PLoS ONE,
doi:10.1371/journal.pone.0113102Enlund-Cerullo, Koljonen, Holmlund-Suila, Hauta-Alus, Rosendahl et al., Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2019-00630Evans, Lippman, Shining Light on the COVID-19 Pandemic: A Vitamin D Receptor Checkpoint in Defense of Unregulated Wound Healing, Cell Metab,
doi:10.1016/j.cmet.2020.09.007Gallelli, Michniewicz, Cione, Squillace, Colosimo et al., 25-Hydroxy Vitamin D detection using different analytic methods in patients with migraine, J. Clin. Med,
doi:10.3390/jcm8060895Gasmi, Tippairote, Mujawdiya, Peana, Menzel et al., Micronutrients as immunomodulatory tools for COVID-19 management, Clin. Immunol,
doi:10.1016/j.clim.2020.108545Glinsky, Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin, D.; Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells, Biomedicines
Grant, 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, Vitamin, Photobiology, metabolism, and clinical application, Endocrinology
Hossein-Nezhad, Spira, Holick, Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: A randomized double-blind clinical trial, PLoS ONE,
doi:10.1371/journal.pone.0058725Jolliffe, Greiller, Mein, Hoti, Bakhsoliani et al., Vitamin D receptor genotype influences risk of upper respiratory infection, Br. J. Nutr,
doi:10.1017/S000711451800209XKarcioglu 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.26409Kotur, 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.2021.689419Luciani, Caroleo, Cannataro, Mirra, D'agostino et al., Immunological Response to SARS-CoV-2 Is Sustained by Vitamin D: A Case Presentation of One-Year Follow-Up, Reports,
doi:10.3390/reports4020018Mcnally, Sampson, Matheson, Hutton, Little, Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: A systematic review and meta-analysis, Pediatric Pulmonol,
doi:10.1002/ppul.22877Mercola, Grant, Wagner, Evidence regarding vitamin D and risk of COVID-19 and its severity, Nutrients,
doi:10.3390/nu12113361Rahmadhani, Zaharan, Mohamed, Moy, Jalaludin, The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country, PLoS ONE,
doi:10.1371/journal.pone.0178695Safar, Chehadeh, Abdel-Wareth, Haq, Jelinek et al., Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus, J. Steroid Biochem. Mol. Biol
Valle, Kim-Schulze, Huang, Beckmann, Nirenberg et al., An inflammatory cytokine signature predicts COVID-19 severity and survival, Nat. Med,
doi:10.1038/s41591-020-1051-9Xie, Wang, Bikle, Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions, Front. Endocrinol,
doi:10.3389/fendo.2020.00040Zhao, Hu, Wang, Mao, Chen et al., Relationship between rs7041 polymorphism of GC gene and serum vitamin D status in Chinese women of childbearing age, J. Hyg. Res
Zhu, Ochalek, Kaufmann, Jones, Deluca, CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo,
doi:10.1073/pnas.1315006110DOI record:
{
"DOI": "10.3390/nu13113680",
"ISSN": [
"2072-6643"
],
"URL": "http://dx.doi.org/10.3390/nu13113680",
"abstract": "<jats:p>Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.</jats:p>",
"alternative-id": [
"nu13113680"
],
"author": [
{
"ORCID": "http://orcid.org/0000-0002-1993-6656",
"affiliation": [],
"authenticated-orcid": false,
"family": "Al-Anouti",
"given": "Fatme",
"sequence": "first"
},
{
"affiliation": [],
"family": "Mousa",
"given": "Mira",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-4225-2746",
"affiliation": [],
"authenticated-orcid": false,
"family": "Karras",
"given": "Spyridon N.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1439-3285",
"affiliation": [],
"authenticated-orcid": false,
"family": "Grant",
"given": "William B.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-6501-7055",
"affiliation": [],
"authenticated-orcid": false,
"family": "Alhalwachi",
"given": "Zainab",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Abdel-Wareth",
"given": "Laila",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1175-4145",
"affiliation": [],
"authenticated-orcid": false,
"family": "Uddin",
"given": "Maimunah",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Alkaabi",
"given": "Nawal",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Tay",
"given": "Guan K.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Mahboub",
"given": "Bassam",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-7141-1438",
"affiliation": [],
"authenticated-orcid": false,
"family": "AlSafar",
"given": "Habiba",
"sequence": "additional"
}
],
"container-title": "Nutrients",
"container-title-short": "Nutrients",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2021,
10,
21
]
],
"date-time": "2021-10-21T01:31:26Z",
"timestamp": 1634779886000
},
"deposited": {
"date-parts": [
[
2021,
10,
25
]
],
"date-time": "2021-10-25T02:29:42Z",
"timestamp": 1635128982000
},
"funder": [
{
"DOI": "10.13039/501100008675",
"award": [
"004"
],
"doi-asserted-by": "publisher",
"name": "Zayed University"
},
{
"DOI": "10.13039/501100004174",
"award": [
"COVID19004"
],
"doi-asserted-by": "publisher",
"name": "Khalifa University of Science and Technology"
}
],
"indexed": {
"date-parts": [
[
2024,
5,
3
]
],
"date-time": "2024-05-03T07:50:10Z",
"timestamp": 1714722610091
},
"is-referenced-by-count": 19,
"issue": "11",
"issued": {
"date-parts": [
[
2021,
10,
20
]
]
},
"journal-issue": {
"issue": "11",
"published-online": {
"date-parts": [
[
2021,
11
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
10,
20
]
],
"date-time": "2021-10-20T00:00:00Z",
"timestamp": 1634688000000
}
}
],
"link": [
{
"URL": "https://www.mdpi.com/2072-6643/13/11/3680/pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1968",
"original-title": [],
"page": "3680",
"prefix": "10.3390",
"published": {
"date-parts": [
[
2021,
10,
20
]
]
},
"published-online": {
"date-parts": [
[
2021,
10,
20
]
]
},
"publisher": "MDPI AG",
"reference": [
{
"key": "ref1",
"unstructured": "WHO Coronavirus (COVID-19) Dashboardhttps://covid19.who.int/"
},
{
"DOI": "10.1038/s41591-020-1051-9",
"doi-asserted-by": "publisher",
"key": "ref2"
},
{
"DOI": "10.1016/j.dsx.2020.05.025",
"doi-asserted-by": "publisher",
"key": "ref3"
},
{
"DOI": "10.1016/j.clim.2020.108545",
"doi-asserted-by": "publisher",
"key": "ref4"
},
{
"DOI": "10.1016/j.cmet.2020.09.007",
"doi-asserted-by": "publisher",
"key": "ref5"
},
{
"DOI": "10.3390/reports4020018",
"doi-asserted-by": "publisher",
"key": "ref6"
},
{
"DOI": "10.3390/biomedicines8050129",
"article-title": "Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin, D.; Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells",
"author": "Glinsky",
"doi-asserted-by": "crossref",
"first-page": "129",
"journal-title": "Biomedicines",
"key": "ref7",
"volume": "8",
"year": "2020"
},
{
"DOI": "10.3389/fnut.2021.689419",
"doi-asserted-by": "publisher",
"key": "ref8"
},
{
"DOI": "10.3390/nu13051714",
"doi-asserted-by": "publisher",
"key": "ref9"
},
{
"DOI": "10.1371/journal.pone.0178695",
"doi-asserted-by": "publisher",
"key": "ref10"
},
{
"DOI": "10.1186/s40246-020-00280-6",
"doi-asserted-by": "publisher",
"key": "ref11"
},
{
"DOI": "10.1016/S0140-6736(20)30633-4",
"doi-asserted-by": "publisher",
"key": "ref12"
},
{
"DOI": "10.1161/CIRCULATIONAHA.120.047659",
"doi-asserted-by": "publisher",
"key": "ref13"
},
{
"DOI": "10.1016/j.jsbmb.2020.105751",
"doi-asserted-by": "publisher",
"key": "ref14"
},
{
"DOI": "10.1016/j.eprac.2021.02.013",
"doi-asserted-by": "publisher",
"key": "ref15"
},
{
"DOI": "10.3390/nu12113361",
"doi-asserted-by": "publisher",
"key": "ref16"
},
{
"DOI": "10.3390/nu12040988",
"doi-asserted-by": "publisher",
"key": "ref17"
},
{
"DOI": "10.1371/journal.pone.0058725",
"doi-asserted-by": "publisher",
"key": "ref18"
},
{
"article-title": "Investigating the association of vitamin D metabolism genes CYP2R1, CYP24A1 and CYP27B1 with vitamin D status in young adult Emiratis",
"author": "Al Anouti",
"first-page": "15",
"journal-title": "J. Food Nutr. Res.",
"key": "ref19",
"volume": "5",
"year": "2017"
},
{
"DOI": "10.1016/j.jsbmb.2017.03.012",
"doi-asserted-by": "publisher",
"key": "ref20"
},
{
"DOI": "10.1016/j.gene.2020.144509",
"doi-asserted-by": "publisher",
"key": "ref21"
},
{
"DOI": "10.1210/jc.2019-00630",
"doi-asserted-by": "publisher",
"key": "ref22"
},
{
"article-title": "Relationship between rs7041 polymorphism of GC gene and serum vitamin D status in Chinese women of childbearing age",
"author": "Zhao",
"first-page": "192",
"journal-title": "Wei Sheng Yan Jiu= J. Hyg. Res.",
"key": "ref23",
"volume": "50",
"year": "2021"
},
{
"DOI": "10.3389/fendo.2020.00040",
"doi-asserted-by": "publisher",
"key": "ref24"
},
{
"DOI": "10.1017/S000711451800209X",
"doi-asserted-by": "publisher",
"key": "ref25"
},
{
"DOI": "10.1002/ppul.22877",
"doi-asserted-by": "publisher",
"key": "ref26"
},
{
"DOI": "10.1002/jmv.26409",
"doi-asserted-by": "publisher",
"key": "ref27"
},
{
"article-title": "Vitamin D: Photobiology, metabolism, and clinical application",
"author": "Holick",
"first-page": "1013",
"journal-title": "Endocrinology",
"key": "ref28",
"volume": "990",
"year": "1995"
},
{
"DOI": "10.1093/hmg/ddq155",
"doi-asserted-by": "publisher",
"key": "ref29"
},
{
"DOI": "10.1016/S0140-6736(10)60635-6",
"doi-asserted-by": "publisher",
"key": "ref30"
},
{
"DOI": "10.1073/pnas.1315006110",
"doi-asserted-by": "publisher",
"key": "ref31"
},
{
"DOI": "10.1371/journal.pone.0113102",
"doi-asserted-by": "publisher",
"key": "ref32"
},
{
"DOI": "10.3390/jcm8060895",
"doi-asserted-by": "publisher",
"key": "ref33"
}
],
"reference-count": 33,
"references-count": 33,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.mdpi.com/2072-6643/13/11/3680"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents",
"type": "journal-article",
"volume": "13"
}
