{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:35:09Z","timestamp":1760146509505,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ernesto Sanchez Villares Foundation","award":["2020\/01"],"award-info":[{"award-number":["2020\/01"]}]},{"name":"Society of Pediatrics of Asturias, Cantabria, and Castilla y Le\u00f3n (SCCALP)","award":["2020\/01"],"award-info":[{"award-number":["2020\/01"]}]},{"name":"Spanish Society of Pediatric Gastroenterology Hepatology and Nutrition (SEGHNP)","award":["2020\/01"],"award-info":[{"award-number":["2020\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives\/Background: Vitamin D-binding protein (VDBP) and free vitamin D are new markers that are being studied as a possible markers of vitamin D status. The main aim of our study was to analyze the VDBP genotype and quantify the levels of free vitamin D in a sample of cystic fibrosis (CF) patients. Methods: We conducted a multicenter, cross-sectional, and prospective study including patients with CF and exocrine pancreatic insufficiency who were clinically stable. We investigated vitamin D levels (total and free) and the different VDBP haplotypes. Free vitamin D levels were measured using an electro-chemiluminescence assay. Results: A sample of 48 patients was obtained (52% male; median age 13.8 years). The most common allele of VDBP was Gc1s (72%) &gt; Gc2 (52%) &gt; Gc1f (27%). The median calcidiol was 21.2 ng\/mL (IR 15.3\u201326.9), and 81% had levels in the insufficiency range: 23 patients (48%) below 20 ng\/mL, and 16 (33%) between 20 and 30 ng\/mL. The median free vitamin D level was 4.2 pg\/mL (IR 3.9\u20135.6). A positive correlation was observed between calcidiol and free vitamin D levels (r = 0.871; p &lt; 0.0001). After adjustment for season, vitamin D supplementation, sex, and CF-related diabetes, patients with Gc1f polymorphism had a lower risk of vitamin D deficiency, OR 0.22 (95% CI 0.05\u20130.99), and p = 0.027. A negative linear trend was observed between the polymorphisms grouped into three categories (Gc1\/Gc1, Gc1\/Gc2, and Gc2\/Gc2, in that order) and vitamin D and free vitamin D levels (p = 0.025 and p = 0.033, respectively). Conclusion: In CF, as in the general population, the most common VDBP haplotype in the Caucasian race is Gc1s. VDBP polymorphisms influence serum vitamin D and free vitamin D levels in CF patients. There is a good correlation between free vitamin D and calcidiol levels, suggesting that measuring the latter in CF does not seem to provide any additional benefit.<\/jats:p>","DOI":"10.3390\/nu16223850","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:46:54Z","timestamp":1731314814000},"page":"3850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polymorphisms of the Vitamin D Binding Protein (VDBP) and Free Vitamin D in Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Paula","family":"Quesada-Colloto","sequence":"first","affiliation":[{"name":"Primary Care Pediatric Service of Principality of Asturias, Centro de Salud de Ventanielles, 33010 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Avello-Llano","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Service, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-1340","authenticated-orcid":false,"given":"Ruth","family":"Garc\u00eda-Romero","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-2043","authenticated-orcid":false,"given":"Mar\u00eda","family":"Garriga-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Section, Hospital Universitario Ram\u00f3n y Cajal, 28080 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"\u00c1lvarez-Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Universitario Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Isabel","family":"Reyes-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Complejo Hospitalario Universitario Insular-Materno Infantil, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Estefan\u00eda","family":"Fern\u00e1ndez-Lorenzo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Teresa Herrera, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8790-1391","authenticated-orcid":false,"given":"Helena","family":"Gil-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Universitario Central de Asturias (HUCA), Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"G\u00f3mez-Alonso","sequence":"additional","affiliation":[{"name":"Clinical Management Unit of Bone Metabolism, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Garc\u00eda-Gil-Albert","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Service, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-8983","authenticated-orcid":false,"given":"Saioa","family":"Vicente-Santamaria","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Ramon y Cajal, 28080 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Pe\u00f1a-Quintana","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, CIBER-OBM ISCIII, Complejo Hospitalario Universitario Insular-Materno Infantil, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jos\u00e9","family":"D\u00edaz-Martin","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ramon","family":"Guti\u00e9rrez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology Section, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0843-2580","authenticated-orcid":false,"given":"Carmen","family":"Martin-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agust\u00edn De la","family":"Mano-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-1821","authenticated-orcid":false,"given":"Ana","family":"Moreno-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Complejo Hospitalario Universitario A Coru\u00f1a, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-9194","authenticated-orcid":false,"given":"David","family":"Gonz\u00e1lez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Section, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S2213-8587(17)30357-1","article-title":"Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials","volume":"5","author":"Autier","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1210\/jcem-63-4-954","article-title":"Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein","volume":"63","author":"Bikle","year":"1986","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1172\/JCI110072","article-title":"Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration","volume":"67","author":"Bouillon","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","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":"Speeckaert","year":"2006","journal-title":"Clin. Chim. Acta."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"981581","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":"ref_6","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa1306357","article-title":"Vitamin D-binding 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_7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1177\/0004563218780135","article-title":"Phenotyping and relative quantification of vitamin D binding protein in a paediatric population by using liquid chromatography-tandem mass spectrometry","volume":"56","author":"Cillero","year":"2019","journal-title":"Ann. Clin. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rozmus, D., Ciesielska, A., P\u0142omi\u0144ski, J., Grzybowski, R., Fiedorowicz, E., Kordulewska, N., Savelkoul, H., Kostyra, E., and Cie\u015bli\u0144ska, 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_9","doi-asserted-by":"crossref","unstructured":"Rozmus, D., P\u0142omi\u0144ski, J., Augustyn, K., and Cie\u015bli\u0144ska, 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_10","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1172\/JCI111617","article-title":"Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease","volume":"74","author":"Bikle","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1210\/jc.2013-3874","article-title":"A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations","volume":"99","author":"Schwartz","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3390\/nu7010443","article-title":"Regulation of calcitriol biosynthesis and activity: Focus on gestational vitamin D deficiency and adverse pregnancy outcomes","volume":"7","author":"Avila","year":"2015","journal-title":"Nutrients"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.endinu.2018.05.002","article-title":"Barcelona longitudinal growth study 1995\u20132017","volume":"65","author":"Carrascosa","year":"2018","journal-title":"Endocrinol. Diabetes Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.clnu.2023.12.017","article-title":"ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis","volume":"43","author":"Wilschanski","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/MAJ.0000000000000592","article-title":"Free 25-Hydroxyvitamin D Concentrations in Cystic Fibrosis","volume":"350","author":"Lee","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cheng, A.C., Duda, S.N., Taylor, R., Delacqua, F., Lewis, A.A., Bosler, T., Johnson, K.B., and Harris, P.A. (2021). REDCap on FHIR: Clinical data interoperability Services. J. Biomed. Inform., 121.","DOI":"10.1016\/j.jbi.2021.103871"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mangas-S\u00e1nchez, C., Garriga-Garc\u00eda, M., Serrano-Nieto, M.J., Garc\u00eda-Romero, R., \u00c1lvarez-Beltr\u00e1n, M., Crehu\u00e1-Gaudiza, E., Mu\u00f1oz-Codoceo, R., Su\u00e1rez-Cortina, L., Vicente-Santamar\u00eda, S., and Mart\u00ednez-Costa, C. (2021). Vitamin D Status in Pediatric and Young Adult Cystic Fibrosis Patients. Are the New Recommendations Effective?. Nutrients, 13.","DOI":"10.3390\/nu13124413"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1016\/j.jcf.2019.08.022","article-title":"Vitamin D deficiency and its treatment in cystic fibrosis","volume":"18","author":"Daley","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mantec\u00f3n, L., Alonso, M.A., Moya, V., Andr\u00e9s, A.G., Avello, N., Mart\u00ednez-Morillo, E., and Santos, F. (2018). Marker of vitamin D status in healthy children: Free or total 25-hydroxyvitamin D?. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202237"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1097\/MPG.0b013e31828f3c05","article-title":"ESPGHAN Committee on Nutrition. Vitamin D in the healthy European paediatric population","volume":"56","author":"Braegger","year":"2013","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1210\/jc.2018-00295","article-title":"Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations","volume":"103","author":"Schwartz","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chun, R.F., Shieh, A., Gottlieb, C., Yacoubian, V., Wang, J., Hewison, M., and Adams, J.S. (2019). Vitamin D Binding Protein and the Biological Activity of Vitamin D. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00718"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.ecl.2017.07.014","article-title":"Genetic and Racial Differences in the Vitamin D Endocrine System","volume":"46","author":"Bouillon","year":"2017","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00223-004-0227-5","article-title":"Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): A cross-sectional study on 595 early postmenopausal women","volume":"77","author":"Lauridsen","year":"2005","journal-title":"Calcif. Tissue Int."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00439-010-0881-9","article-title":"Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects","volume":"128","author":"Bu","year":"2010","journal-title":"Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Usategui-Mart\u00edn, R., De Luis-Rom\u00e1n, D.A., Fern\u00e1ndez-G\u00f3mez, J.M., Ruiz-Mambrilla, M., and P\u00e9rez-Castrill\u00f3n, J.L. (2022). Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients, 14.","DOI":"10.3390\/nu14020360"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.clnesp.2022.07.018","article-title":"FIRST Study Group. Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements","volume":"51","author":"Lai","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.jcf.2024.02.005","article-title":"Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis","volume":"23","author":"Braun","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJMoa2100665","article-title":"VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes","volume":"385","author":"Barry","year":"2021","journal-title":"N. Engl. J. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/22\/3850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:29:57Z","timestamp":1760113797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/22\/3850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":30,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["nu16223850"],"URL":"https:\/\/doi.org\/10.3390\/nu16223850","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2024,11,11]]}}}