{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:35Z","timestamp":1760145635631,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center of Poland","award":["2011\/03\/B\/NZ7\/06550"],"award-info":[{"award-number":["2011\/03\/B\/NZ7\/06550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&amp;RT). The relationship between the concentration\/dose (C\/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C\/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C\/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients.<\/jats:p>","DOI":"10.3390\/jcm13164966","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:53:19Z","timestamp":1724417599000},"page":"4966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Vitamin D Metabolism Genes and Their Genomic Background in Shaping Cyclosporine A Dosage Parameters after Kidney Transplantation"],"prefix":"10.3390","volume":"13","author":[{"given":"Katarzyna","family":"Kotowska","sequence":"first","affiliation":[{"name":"Clinic of Maxillofacial Surgery, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartosz","family":"Wojciuk","sequence":"additional","affiliation":[{"name":"Department of Immunological Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-7489","authenticated-orcid":false,"given":"Jerzy","family":"Sie\u0144ko","sequence":"additional","affiliation":[{"name":"Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5455-8315","authenticated-orcid":false,"given":"Anna","family":"Bogacz","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Cell Therapy, Regional Blood Center, 60-354 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iga","family":"Stukan","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-2696","authenticated-orcid":false,"given":"Sylwester","family":"Dro\u017cd\u017cal","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogus\u0142aw","family":"Czerny","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karol","family":"Tejchman","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3900-4901","authenticated-orcid":false,"given":"Grzegorz","family":"Trybek","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Dentistry, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogus\u0142aw","family":"Machali\u0144ski","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-0156","authenticated-orcid":false,"given":"Maciej","family":"Kotowski","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Transplantation, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/13102818.2014.995415","article-title":"Relationship between Vitamin D Status and Immunosuppressive Therapy in Kidney Transplant Recipients","volume":"29","author":"Filipov","year":"2015","journal-title":"Biotechnol. 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