{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:02:30Z","timestamp":1779879750034,"version":"3.53.1"},"update-to":[{"DOI":"10.12688\/f1000research.160839.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000}}],"reference-count":32,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Africa Center of Excellence in Materials, Product Development and Nanotechnology (MAPRONANO ACE) Makerere University"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Tuberculosis remains a significant global public health concern. Genetic variants influence the distribution of vitamin D in circulation, leading to vitamin D deficiency. The two extensively studied non-synonymous D-binding protein nucleotide polymorphisms rs7041 and rs4588 were found in different populations. These polymorphisms result into three different genotypes, Gc1F (rs7041(A)- rs4588(G)), Gc1S (rs7041(C)- rs4588(G)) and Gc2 (rs7041(A)- rs4588(T)). These genotypes have configurational changes that differ and therefore cause variation in the binding affinity of the vitamin D metabolite. This study aimed to compare the frequency distribution of vitamin D binding protein gene polymorphisms in patients with active Ugandan tuberculosis, individuals with latent tuberculosis infection, and those with no tuberculosis infection. Methods This pilot studyselected 102 samples, including 52 active tuberculosis patients, 23 latent tuberculosis individuals, and 27 individuals without tuberculosis infection, from a previous cross-sectional study. Vitamin D binding protein rs7041 and rs4588 SNPs were genotyped using Polymerase Chain Reaction and Sanger sequencing. Vitamin D binding protein gene polymorphisms were identified using BioEdit software. 7.2 (http:\/\/www.mbio.ncsu.edu\/BioEdit\/bioedit.html) Results This study revealed no significant differences in DBP genetic polymorphisms among the study groups. The frequency distribution of the DBP gene has been reported to be 97% Gc1F, 2% Gc2, and 1% Gc1S. The frequency distribution among patients with TB was 96.2% for Gc1F, 0% for Gc1F, and 3.8% for Gc2. Among the LTBI cases, 95.7% were Gc1F, 4.3% were Gc1S, and 0%were Gc2. The Hardy-Weinberg equilibrium analysis was in equilibrium, D\u2019= 0. P=0.2 Conclusions The Gc1F genotype was predominantly found in the study population, with no difference in the frequency distribution according to TB status.<\/ns3:p>","DOI":"10.12688\/f1000research.160839.2","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T12:35:09Z","timestamp":1747830909000},"page":"154","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D binding protein rs7041 and rs4588 gene polymorphisms in Ugandan tuberculosis patients and household contacts: A pilot study"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-4643","authenticated-orcid":false,"given":"Acen L.","family":"Ester","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Biomedical Sciences, College of Health Sciences Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joloba L.","family":"Moses","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of\u00a0Health Sciences Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Akintola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Convergence Science and Technology, School of Industrial Technology Advances Daegu 41566 Kyungpook National University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwana","family":"Begum Syed Nabi","sequence":"additional","affiliation":[{"name":"Department of Southern Area Crop Science Miryang 50424 National Institute of Crop Science, Rural Development Administration"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8303-6046","authenticated-orcid":false,"given":"Irene","family":"Andia Biraro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, College of Health Sciences Unit Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Worodria","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pulmonary Division Kampala Mulago National Referral Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Okeng","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biotechnology, School of Bio-security and Laboratory Sciences, College of Veterinary Medicine Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Bwambale","sequence":"additional","affiliation":[{"name":"Department of Biosecurity Ecosystems and Veterinary Public Health , School of Bio-security and Laboratory Sciences, College of Veterinary Medicine Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudarshiru","family":"Bbuye","sequence":"additional","affiliation":[{"name":"Makerere Lung Institute, College of Health Sciences Kampala POBOX 7072 Makerere University College of Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Patrick Kateete","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of\u00a0Health Sciences Kampala POBOX 7072 Makerere University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref26","doi-asserted-by":"publisher","first-page":"5296","DOI":"10.1038\/s41598-022-09375-7","article-title":"Hypovitaminosis D among newly diagnosed pulmonary TB patients and their household contacts in Uganda.","volume":"12","author":"E Acen","year":"2022","journal-title":"Sci. Rep."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/1756-0500-6-293","article-title":"Vitamin D deficiency among adult patients with tuberculosis: a cross sectional study from a national referral hospital in Uganda.","volume":"6","author":"D Kibirige","year":"2013","journal-title":"BMC Res. Notes."},{"key":"ref1","doi-asserted-by":"publisher","first-page":"33-42","DOI":"10.1016\/j.cca.2006.03.011","article-title":"Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism.","volume":"372","author":"M Speeckaert","year":"2006","journal-title":"Clin. Chim. Acta."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e0173695","DOI":"10.1371\/journal.pone.0173695","article-title":"Genetic variant in vitamin D-binding protein is associated with metabolic syndrome and lower 25-hydroxyvitamin D levels in polycystic ovary syndrome: A cross-sectional study.","volume":"12","author":"Santos","year":"2017","journal-title":"PLoS One."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1-7","DOI":"10.1186\/s43042-020-00076-2","article-title":"Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population.","volume":"21","author":"B Alhomsi","year":"2020","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"662-669","DOI":"10.1038\/s41390-019-0322-y","article-title":"Vitamin D binding protein polymorphisms significantly impact vitamin D status in children.","volume":"86","author":"E Newton","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1-6","DOI":"10.1155\/2014\/981581","article-title":"Vitamin D binding protein impact on 25-hydroxyvitamin D levels under different physiologic and pathologic conditions.","volume":"2014","author":"Yousefzadeh","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref6","first-page":"115-129","article-title":"Immunomodulatory role of vitamin D in infectious and non-infectious diseases.","volume":"6","author":"M Rehan","year":"2019","journal-title":"Hosts Viruses."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1232-1240","DOI":"10.3945\/ajcn.115.107334","article-title":"Race, vitamin D\u2013binding protein gene polymorphisms, 25-hydroxyvitamin D, and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.","volume":"101","author":"J Reis","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3389\/fendo.2019.00317","article-title":"Vitamin D binding protein, total and free vitamin D levels in different physiological and pathophysiological conditions.","volume":"10","author":"Bikle","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"329-335","DOI":"10.1055\/s-2006-924256","article-title":"Vitamin D-binding protein (DBP) gene polymorphism is associated with Graves\u2019 disease and the vitamin D status in a Polish population study.","volume":"114","author":"A Kurylowicz","year":"2006","journal-title":"Exp. Clin. Endocrinol. Diabetes."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2226-2234","DOI":"10.1210\/jc.2016-1104","article-title":"Free 25-hydroxyvitamin D: impact of vitamin D binding protein assays on racial-genotypic associations.","volume":"101","author":"Nielson","year":"2016","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"166-170","DOI":"10.1016\/j.bone.2014.12.068","article-title":"Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.","volume":"74","author":"Braithwaite","year":"2015","journal-title":"Bone."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"132-137","DOI":"10.1016\/j.jsbmb.2013.09.012","article-title":"Vitamin D and DBP: The free hormone hypothesis revisited.","volume":"144","author":"Chun","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref13","first-page":"1409-1413","article-title":"The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate.","volume":"93","author":"L Karcioglu Batur","year":"2021"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"853-855","DOI":"10.3201\/eid1605.091693","article-title":"Vitamin D deficiency and tuberculosis progression.","volume":"16","author":"N Talat","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01048","article-title":"Methylation of the Vitamin D Receptor (VDR) Gene, Together with Genetic Variation, Race, and Environment Influence the Signaling Efficacy of the Toll-Like Receptor 2\/1-VDR Pathway.","volume":"8","author":"V Meyer","year":"2017","journal-title":"Front. Immunol."},{"key":"ref16","first-page":"564229","article-title":"Allele frequency distribution of SNPs associated with levels of Vitamin D-binding protein and 25-hydroxyvitamin D.","author":"I Nizamutdinov","year":"2019","journal-title":"bioRxiv."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0272788","DOI":"10.1371\/journal.pone.0272788","article-title":"Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda.","volume":"17","author":"E Acen","year":"2022","journal-title":"PLoS One."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1991-2000","DOI":"10.1056\/NEJMoa1306357","article-title":"Vitamin D\u2013binding protein and vitamin D status of black Americans and white Americans.","volume":"369","author":"C Powe","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1-14","DOI":"10.1186\/s12916-021-01985-8","article-title":"Prevalence and predictors of vitamin D deficiency in young African children.","volume":"19","author":"R Mogire","year":"2021","journal-title":"BMC Med."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1106-1112","DOI":"10.1183\/09031936.00087009","article-title":"Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.","volume":"35","author":"Martineau","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1-9","DOI":"10.1186\/s40795-016-0085-3","article-title":"Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians\u2013a cross-sectional study.","volume":"2","author":"E Saarnio","year":"2016","journal-title":"BMC Nutrition."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12890-016-0240-2","article-title":"Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not.","volume":"16","author":"K Junaid","year":"2016","journal-title":"BMC Pulm. Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1106-1112","DOI":"10.1183\/09031936.00087009","article-title":"Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.","volume":"35","author":"A Martineau","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"148-154","DOI":"10.1016\/j.nut.2019.02.003","article-title":"Efficacy of vitamin D supplementation according to vitamin D-binding protein polymorphisms.","volume":"63-64","author":"N Al-Daghri","year":"2019","journal-title":"Nutrition."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"4626-4632","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":"S Alharazy","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"100822","DOI":"10.1016\/j.mgene.2020.100822","article-title":"Association of rs7041 and rs4588 polymorphisms of vitamin D binding protein gene in pulmonary tuberculosis.","volume":"26","author":"M Harishankar","year":"2020","journal-title":"Meta Gene."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"166-170","DOI":"10.1016\/j.bone.2014.12.068","article-title":"Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.","volume":"74","author":"V Braithwaite","year":"2015","journal-title":"Bone."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12916-021-01985-8","article-title":"Prevalence and predictors of vitamin D deficiency in young African children.","volume":"19","author":"R Mogire","year":"2021","journal-title":"BMC Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s40795-016-0085-3","article-title":"Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians \u2013 a cross-sectional study.","volume":"2","author":"E Saarnio","year":"2016","journal-title":"BMC Nutr."},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.28234484.v3","author":"E Acen","year":"2025","journal-title":"figshare."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-154\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-154\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-154\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:09:28Z","timestamp":1779876568000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-154\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":32,"URL":"https:\/\/doi.org\/10.12688\/f1000research.160839.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.160839.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.182062.r386374","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.182062.r434456","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.182062.r434456","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.182062.r386374","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-154\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.182062.r386374, Dina Keumala Sari, Department of Nutrition, Faculty of Medicine, Universitas Sumatera Utara, Medan, 24 Jun 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-154\/v2#referee-response-386374","order":0,"name":"referee-response-386374","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.176796.r369604, Ramalingam Bethunaickan, ICMR-National Institute for Research in Tuberculosis, Chennai, 13 Mar 2025, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-154\/v1#referee-response-369604","order":1,"name":"referee-response-369604","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.182062.r434456, Habtamu Milkias Wolde, School of Medicine, Department of Precision Medicine, SungKyunKwan University, Suwon, Seoul, 11 Dec 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-154\/v2#referee-response-434456","order":2,"name":"referee-response-434456","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by \u201cThe Africa Center of Excellence in Materials, Product Development and Nanotechnology (MAPRONANO ACE) Makerere University\u201d under the World Bank project.  The funding agencies did not play any role in the development of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}