{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:04:56Z","timestamp":1792047896633,"version":"4.4.0"},"reference-count":30,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C&gt;T, 1236C&gt;T, 2677G&gt;T\/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1\u201314 days, 15\u201330 days, 31\u201360 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T\/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T\/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.<\/jats:p>","DOI":"10.3390\/ijms252010999","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:02:58Z","timestamp":1728878578000},"page":"10999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients"],"prefix":"10.3390","volume":"25","author":[{"given":"Corina Andreea","family":"Rotarescu","sequence":"first","affiliation":[{"name":"Department of Immunology and Transplant Immunology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"Department of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4284-8654","authenticated-orcid":false,"given":"Ion","family":"Maruntelu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Transplant Immunology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"Department of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ion","family":"Rotarescu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, \u201cProf. Dr. C. C. Iliescu\u201d Emergency Institute for Cardiovascular Diseases, 258 Fundeni Avenue, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra-Elena","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Transplant Immunology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-2694","authenticated-orcid":false,"given":"Ileana","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Transplant Immunology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"Department of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, 022328 Bucharest, Romania"},{"name":"Academy of Romanian Scientists (AOSR), 3 Ilfov Street, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.kint.2019.07.012","article-title":"A Single Number for Advocacy and Communication-Worldwide More than 850 Million Individuals Have Kidney Diseases","volume":"96","author":"Jager","year":"2019","journal-title":"Kidney Int."},{"key":"ref_2","first-page":"213","article-title":"Chronic Kidney Disease and End-Stage Renal Disease-a Review Produced to Contribute to the Report \u201cthe Status of Health in the European Union: Towards a Healthier Europe","volume":"3","author":"Zoccali","year":"2010","journal-title":"\u201d NDT Plus"},{"key":"ref_3","unstructured":"Hashmi, M.F., Benjamin, O., and Lappin, S.L. (2024). End-Stage Renal Disease. StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1053\/j.ajkd.2009.09.035","article-title":"Prevalence of CKD and Comorbid Illness in Elderly Patients in the United States: Results from the Kidney Early Evaluation Program (KEEP)","volume":"55","author":"Stevens","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ki.2009.377","article-title":"KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients: A Summary","volume":"77","author":"Kasiske","year":"2010","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1097\/00007890-200105150-00021","article-title":"The Effect of Gut Metabolism on Tacrolimus Bioavailability in Renal Transplant Recipients","volume":"71","author":"Tuteja","year":"2001","journal-title":"Transplantation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/j.1552-4604.1994.tb02052.x","article-title":"Pharmacokinetics of FK506 after Intravenous and Oral Administration in Patients Awaiting Renal Transplantation","volume":"34","author":"Gruber","year":"1994","journal-title":"J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.clpt.2005.09.013","article-title":"Intestinal MDR1\/ABCB1 Level at Surgery as a Risk Factor of Acute Cellular Rejection in Living-Donor Liver Transplant Patients","volume":"79","author":"Masuda","year":"2006","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0021-9258(19)75806-2","article-title":"The Human Multidrug Resistance (MDR1) Gene. cDNA Cloning and Transcription Initiation","volume":"262","author":"Ueda","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/10915810600746023","article-title":"Structure, Function, Expression, Genomic Organization, and Single Nucleotide Polymorphisms of Human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) Efflux Transporters","volume":"25","author":"Choudhuri","year":"2006","journal-title":"Int. J. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7735","DOI":"10.1073\/pnas.84.21.7735","article-title":"Cellular Localization of the Multidrug-Resistance Gene Product P-Glycoprotein in Normal Human Tissues","volume":"84","author":"Thiebaut","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20383","DOI":"10.1016\/S0021-9258(19)88713-6","article-title":"Functional Involvement of P-Glycoprotein in Blood-Brain Barrier","volume":"267","author":"Tatsuta","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1073\/pnas.86.2.695","article-title":"Multidrug-Resistance Gene (P-Glycoprotein) Is Expressed by Endothelial Cells at Blood-Brain Barrier Sites","volume":"86","author":"Casals","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Andersen, V., Vogel, U., Godiksen, S., Frenzel, F.B., S\u00e6b\u00f8, M., Hamfjord, J., Kure, E., and Vogel, L.K. (2013). Low ABCB1 Gene Expression Is an Early Event in Colorectal Carcinogenesis. PLoS ONE, 8.","DOI":"10.1371\/annotation\/7cd6c6a6-b281-4bf3-b478-a289ed39b375"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1463-1318.2012.02919.x","article-title":"ABCB1\/MDR1 Gene Polymorphism and Colorectal Cancer Risk: A Meta-Analysis of Case-Control Studies","volume":"15","author":"He","year":"2013","journal-title":"Color. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/bdd.1881","article-title":"ABCB1 Haplotype Influences the Sirolimus Dose Requirements in Chinese Renal Transplant Recipients","volume":"35","author":"Lee","year":"2014","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_17","first-page":"165","article-title":"Use of Diplotypes\u2014Matched Haplotype Pairs from Homologous Chromosomes\u2014In Gene-Disease Association Studies","volume":"26","author":"Zuo","year":"2014","journal-title":"Shanghai Arch Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1089\/dna.2009.0953","article-title":"Haplotype-Based Analysis of MDR1\/ABCB1 Gene Polymorphisms in a Turkish Population","volume":"29","year":"2010","journal-title":"DNA Cell Biol."},{"key":"ref_19","unstructured":"(2024, July 24). Home\u2014SNP\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev.pharmtox.43.100901.140233","article-title":"Genetic Polymorphisms of the Human MDR1 Drug Transporter","volume":"43","author":"Schwab","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1517\/17425247.3.1.23","article-title":"Single Nucleotide Polymorphisms in Human P-Glycoprotein: Its Impact on Drug Delivery and Disposition","volume":"3","author":"Dey","year":"2006","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1517\/phgs.4.4.397.22747","article-title":"Pharmacogenetics of MDR1 and Its Impact on the Pharmacokinetics and Pharmacodynamics of Drugs","volume":"4","author":"Sakaeda","year":"2003","journal-title":"Pharmacogenomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00228-011-1182-5","article-title":"Clinical and Genetic Factors Affecting Tacrolimus Trough Levels and Drug-Related Outcomes in Korean Kidney Transplant Recipients","volume":"68","author":"Kim","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/01.tp.0000234942.78716.c0","article-title":"Multidrug Resistance Gene-1 (MDR-1) Haplotypes Have a Minor Influence on Tacrolimus Dose Requirements","volume":"82","author":"Fredericks","year":"2006","journal-title":"Transplantation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.transproceed.2006.02.079","article-title":"The Effect of MDR1 (ABCB1) Polymorphism on the Pharmacokinetic of Tacrolimus in Turkish Renal Transplant Recipients","volume":"38","author":"Akbas","year":"2006","journal-title":"Transplant. Proc."},{"key":"ref_26","first-page":"1093","article-title":"Influence of CYP3A5 and ABCB1 Gene Polymorphisms and Other Factors on Tacrolimus Dosing in Caucasian Liver and Kidney Transplant Patients","volume":"28","author":"Provenzani","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1139\/cjpp-2013-0128","article-title":"Pharmacogenotyping of CYP3A5 in Predicting Dose-Adjusted Trough Levels of Tacrolimus among Malaysian Kidney-Transplant Patients","volume":"92","author":"Hamzah","year":"2014","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.transproceed.2011.11.004","article-title":"Impact of Cytochrome P450 3A and ATP-Binding Cassette Subfamily B Member 1 Polymorphisms on Tacrolimus Dose-Adjusted Trough Concentrations among Korean Renal Transplant Recipients","volume":"44","author":"Cho","year":"2012","journal-title":"Transplant. Proc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/FTD.0b013e31819c6a37","article-title":"Multi-Site Analytical Evaluation of the Abbott ARCHITECT Tacrolimus Assay","volume":"31","author":"Wallemacq","year":"2009","journal-title":"Ther. Drug Monit."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jclinepi.2014.03.012","article-title":"False Discovery Rate Control Is a Recommended Alternative to Bonferroni-Type Adjustments in Health Studies","volume":"67","author":"Glickman","year":"2014","journal-title":"J. Clin. 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