{"title":"CYP3A5 基因多态性对同种异体造血干细胞移植患者他克莫司血药浓度和不良事件的影响","authors":"","doi":"10.1016/j.transproceed.2024.08.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Tacrolimus is the core basic immunosuppressant after transplantation. Cytochrome P450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The aim of this study was to investigate the effect of CYP3A5 gene polymorphisms on tacrolimus blood concentrations and acute graft versus host disease (GVHD) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p></div><div><h3>Methods</h3><p>This study included adult patients who received allo-HSCT at the First Affiliated Hospital of Wannan Medical College from January 2021 to June 2022, and received postoperative treatment with tacrolimus. Tacrolimus blood levels were obtained by fully automatic chemiluminescence immunoassay analyzer. Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 allelic variants.</p></div><div><h3>Results</h3><p>In a total of 50 transplant patients, 30 patients were detected with CYP3A5*3/*3 genotype, 15 patients with CYP3A5*1/*3 genotype, and 5 patients with CYP3A5*1/*1 genotype. The initial tacrolimus blood concentrations in allo-HSCT patients with CYP3A5*1/*1, *1/*3, and *3/*3 genes were 7.75, 8.61, and 10.19 ng/mL, respectively; The initial blood concentration/dose (C/D) ratios were 4.08, 4.42 and 5.66 ng/(mL·mg), respectively. The C/D ratios of allo-HSCT patients carrying CYP3A5*1/*1, *1/*3, and *3/*3 genes were 4.35 and 4.71 and 5.58, 4.19, 4.56 and 5.71 ng/(mL·mg) in the second and 3rd weeks after operation. These results showed that the blood concentration and C/D ratio of tacrolimus in patients with CYP3A5*3/*3 genotype were significantly higher than those in patients with CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Moreover, the incidence of acute GVHD after allo-HSCT in patients with CYP3A5*1/*1 genotype was significantly higher than that in patients with CYP3A5*1/*3 or CYP3A5*3/*3 genotype.</p></div><div><h3>Conclusions</h3><p>Most patients carry the mutant allele CYP3A5*3. CYP3A5 gene polymorphisms affect tacrolimus blood concentrations and acute GVHD after allo-HSCT.</p></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of CYP3A5 Gene Polymorphisms on Tacrolimus Blood Concentrations and Adverse Events in Allogeneic Hematopoietic Stem Cell Transplant Patients\",\"authors\":\"\",\"doi\":\"10.1016/j.transproceed.2024.08.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Tacrolimus is the core basic immunosuppressant after transplantation. Cytochrome P450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The aim of this study was to investigate the effect of CYP3A5 gene polymorphisms on tacrolimus blood concentrations and acute graft versus host disease (GVHD) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p></div><div><h3>Methods</h3><p>This study included adult patients who received allo-HSCT at the First Affiliated Hospital of Wannan Medical College from January 2021 to June 2022, and received postoperative treatment with tacrolimus. Tacrolimus blood levels were obtained by fully automatic chemiluminescence immunoassay analyzer. Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 allelic variants.</p></div><div><h3>Results</h3><p>In a total of 50 transplant patients, 30 patients were detected with CYP3A5*3/*3 genotype, 15 patients with CYP3A5*1/*3 genotype, and 5 patients with CYP3A5*1/*1 genotype. The initial tacrolimus blood concentrations in allo-HSCT patients with CYP3A5*1/*1, *1/*3, and *3/*3 genes were 7.75, 8.61, and 10.19 ng/mL, respectively; The initial blood concentration/dose (C/D) ratios were 4.08, 4.42 and 5.66 ng/(mL·mg), respectively. The C/D ratios of allo-HSCT patients carrying CYP3A5*1/*1, *1/*3, and *3/*3 genes were 4.35 and 4.71 and 5.58, 4.19, 4.56 and 5.71 ng/(mL·mg) in the second and 3rd weeks after operation. These results showed that the blood concentration and C/D ratio of tacrolimus in patients with CYP3A5*3/*3 genotype were significantly higher than those in patients with CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Moreover, the incidence of acute GVHD after allo-HSCT in patients with CYP3A5*1/*1 genotype was significantly higher than that in patients with CYP3A5*1/*3 or CYP3A5*3/*3 genotype.</p></div><div><h3>Conclusions</h3><p>Most patients carry the mutant allele CYP3A5*3. CYP3A5 gene polymorphisms affect tacrolimus blood concentrations and acute GVHD after allo-HSCT.</p></div>\",\"PeriodicalId\":23246,\"journal\":{\"name\":\"Transplantation proceedings\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplantation proceedings\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041134524004378\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation proceedings","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041134524004378","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Effect of CYP3A5 Gene Polymorphisms on Tacrolimus Blood Concentrations and Adverse Events in Allogeneic Hematopoietic Stem Cell Transplant Patients
Background
Tacrolimus is the core basic immunosuppressant after transplantation. Cytochrome P450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The aim of this study was to investigate the effect of CYP3A5 gene polymorphisms on tacrolimus blood concentrations and acute graft versus host disease (GVHD) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods
This study included adult patients who received allo-HSCT at the First Affiliated Hospital of Wannan Medical College from January 2021 to June 2022, and received postoperative treatment with tacrolimus. Tacrolimus blood levels were obtained by fully automatic chemiluminescence immunoassay analyzer. Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 allelic variants.
Results
In a total of 50 transplant patients, 30 patients were detected with CYP3A5*3/*3 genotype, 15 patients with CYP3A5*1/*3 genotype, and 5 patients with CYP3A5*1/*1 genotype. The initial tacrolimus blood concentrations in allo-HSCT patients with CYP3A5*1/*1, *1/*3, and *3/*3 genes were 7.75, 8.61, and 10.19 ng/mL, respectively; The initial blood concentration/dose (C/D) ratios were 4.08, 4.42 and 5.66 ng/(mL·mg), respectively. The C/D ratios of allo-HSCT patients carrying CYP3A5*1/*1, *1/*3, and *3/*3 genes were 4.35 and 4.71 and 5.58, 4.19, 4.56 and 5.71 ng/(mL·mg) in the second and 3rd weeks after operation. These results showed that the blood concentration and C/D ratio of tacrolimus in patients with CYP3A5*3/*3 genotype were significantly higher than those in patients with CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Moreover, the incidence of acute GVHD after allo-HSCT in patients with CYP3A5*1/*1 genotype was significantly higher than that in patients with CYP3A5*1/*3 or CYP3A5*3/*3 genotype.
Conclusions
Most patients carry the mutant allele CYP3A5*3. CYP3A5 gene polymorphisms affect tacrolimus blood concentrations and acute GVHD after allo-HSCT.
期刊介绍：
Transplantation Proceedings publishes several different categories of manuscripts, all of which undergo extensive peer review by recognized authorities in the field prior to their acceptance for publication.
The first type of manuscripts consists of sets of papers providing an in-depth expression of the current state of the art in various rapidly developing components of world transplantation biology and medicine. These manuscripts emanate from congresses of the affiliated transplantation societies, from Symposia sponsored by the Societies, as well as special Conferences and Workshops covering related topics.
Transplantation Proceedings also publishes several special sections including publication of Clinical Transplantation Proceedings, being rapid original contributions of preclinical and clinical experiences. These manuscripts undergo review by members of the Editorial Board.
Original basic or clinical science articles, clinical trials and case studies can be submitted to the journal?s open access companion title Transplantation Reports.
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