{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:56:29Z","timestamp":1781927789370,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s\/2 (35.3%) and Gc1s\/1s (31.4%), and Gc1f\/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19.<\/jats:p>","DOI":"10.3390\/metabo11100696","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Vitamin-D Binding Protein Gene Polymorphisms and Serum 25-Hydroxyvitamin-D in a Turkish Population"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-9137","authenticated-orcid":false,"given":"Lutfiye","family":"Karc\u0131o\u011flu Batur","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul 34010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-3053","authenticated-orcid":false,"given":"Ahmet","family":"\u00d6zayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat Emrah","family":"Mavi\u015f","sequence":"additional","affiliation":[{"name":"Sem Laboratuar Cihazlari Pazarlama San. ve Tic. Inc., R&D Center, Istanbul 34746, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6k\u00e7e G\u00f6ksu","family":"G\u00fcrsu","sequence":"additional","affiliation":[{"name":"Sem Laboratuar Cihazlari Pazarlama San. ve Tic. Inc., R&D Center, Istanbul 34746, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Harbige","sequence":"additional","affiliation":[{"name":"Lipidomics and Nutrition Research Centre, School of Human Sciences, London Metropolitan University, London N7 8DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezih","family":"Hekim","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul 34010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1002\/jbmr.387","article-title":"Vitamin D\u2013binding protein modifies the vitamin D\u2013bone mineral density relationship","volume":"26","author":"Powe","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1210\/edrv-10-3-232","article-title":"The free hormone hypothesis: A physiologically based mathematical model","volume":"10","author":"Mendel","year":"1989","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1210\/endo-124-2-649","article-title":"Free, and not total, 1,25-dihydroxyvitamin d regulates 25-hydroxyvitamin d metabolism by keratinocytes","volume":"124","author":"Bikle","year":"1989","journal-title":"Endocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI5244","article-title":"Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein","volume":"103","author":"Safadi","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/MNH.0b013e328346d6ba","article-title":"Determinants of vitamin D status: Focus on genetic variations","volume":"20","author":"Berry","year":"2011","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0140-6736(10)60588-0","article-title":"Common genetic determinants of vitamin D insufficiency: A genome-wide association study","volume":"376","author":"Wang","year":"2010","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"148","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":"Mohammed","year":"2019","journal-title":"Nutrition"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","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":"ref_10","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1017\/S0007114517000538","article-title":"Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes","volume":"117","author":"Petersen","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_11","unstructured":"Leblanc, E., Chou, R., Zakher, B., Daeges, M., and Pappas, M. (2020, August 11). Screening for Vitamin D Deficiency: Systematic Review for the U.S. Preventive Services Task Force Recommendation, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK263420\/."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","unstructured":"Hekimsoy, Z., Din\u00e7, G., Kafes\u00e7iler, S., Onur, E., G\u00fcven\u00e7, Y., Pala, T., G\u00fc\u00e7l\u00fc, F., and \u00d6zmen, B. (2010). Vitamin D status among adults in the Aegean region of Turkey. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-782"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1136\/thx.2009.128793","article-title":"The vitamin D axis in the lung: A key role for vitamin D-binding protein","volume":"65","author":"Chishimba","year":"2010","journal-title":"Thorax"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1136\/thx.2010.140921","article-title":"Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages","volume":"66","author":"Wood","year":"2011","journal-title":"Thorax"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s40279-017-0841-9","article-title":"Vitamin D and the Athlete: Current Perspectives and New Challenges","volume":"48","author":"Owens","year":"2018","journal-title":"Sports Med."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000348847","article-title":"Variations in the vitamin d-binding protein (DBP) gene are related to lower 25-hydroxyvitamin d levels in healthy girls: A cross-sectional study","volume":"79","author":"Santos","year":"2013","journal-title":"Horm. Res. Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11152","DOI":"10.3748\/wjg.v21.i39.11152","article-title":"Serum vitamin D3does not correlate with liver fibrosis in chronic hepatitis C","volume":"21","author":"Ren","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/ng.876","article-title":"Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers","volume":"43","author":"Miki","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1665-2681(19)31357-2","article-title":"Vitamin D deficiency and vitamin D therapy in chronic hepatitis C","volume":"12","author":"Ladero","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.21103\/Article6(4)_OA3","article-title":"Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4","volume":"6","author":"Shehab","year":"2016","journal-title":"Int. J. Biomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1016\/j.clnu.2017.10.024","article-title":"Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women","volume":"37","author":"Shao","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e9881","DOI":"10.1097\/MD.0000000000009881","article-title":"Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients","volume":"97","author":"Scalioni","year":"2018","journal-title":"Medicine"},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S8756-3282(02)00692-0","article-title":"Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III","volume":"30","author":"Looker","year":"2002","journal-title":"Bone"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0140-6736(95)91266-5","article-title":"Serum vitamin D concentrations among elderly people in Europe","volume":"346","author":"Berg","year":"1995","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/ajcn\/85.3.860","article-title":"Hypovitaminosis D in British adults at age 45 y: Nationwide cohort study of dietary and lifestyle predictors","volume":"85","author":"Power","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","first-page":"1745","article-title":"Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey","volume":"22","author":"Farwell","year":"2010","journal-title":"Osteoporos. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa1306357","article-title":"Vitamin D\u2013Binding Protein and Vitamin D Status of Black Americans and White Americans","volume":"369","author":"Powe","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2226","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. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1373\/clinchem.2015.244541","article-title":"Measurement by a novel LC-MS\/MS methodology reveals similar serum concentrations of vitamin D\u2013binding protein in blacks and whites","volume":"62","author":"Henderson","year":"2016","journal-title":"Clin. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.2147\/COPD.S234464","article-title":"Sputum Vitamin D Binding Protein (VDBP) GC1S\/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD","volume":"15","author":"Gao","year":"2020","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJMc1502602","article-title":"Vitamin D\u2013Binding Protein Concentrations Quantified by Mass Spectrometry","volume":"373","author":"Hoofnagle","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.5740\/jaoacint.17-0084","article-title":"A direct assay for measuring free 25-hydroxyvitamin D","volume":"100","author":"Heureux","year":"2017","journal-title":"J. AOAC Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0126359","DOI":"10.1371\/journal.pone.0126359","article-title":"The DBP phenotype Gc-1f\/Gc-1f is associated with reduced risk of cancer. The Troms\u00f8 Study","volume":"10","author":"Jorde","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pekkinen, M., Saarnio, E., Viljakainen, H.T., Kokkonen, E., Jakobsen, J., Cashman, K., M\u00e4kitie, O., and Lamberg-Allardt, C. (2014). Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in finland. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087292"},{"key":"ref_39","first-page":"451","article-title":"Vitamin-D deficiency is more common in UK black people and a possible COVID-19 risk factor","volume":"21","author":"Harbige","year":"2021","journal-title":"Ann. Nutr. Metab."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"374","DOI":"10.21037\/atm.2019.07.49","article-title":"Vitamin D-binding protein (rs4588) T\/T genotype is associated with anteroseptal myocardial infarction in coronary artery disease patients","volume":"7","year":"2019","journal-title":"Ann. Transl. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/696\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:11:52Z","timestamp":1760166712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["metabo11100696"],"URL":"https:\/\/doi.org\/10.3390\/metabo11100696","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}