Effect of CYP3A422, CYP3A53 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI:10.1097/FPC.0000000000000516

Abdel-Hameed Im Ebid, Dina A Ismail, Neama M Lotfy, Mohamed A Mahmoud, Magdy El-Sharkawy

{"title":"Effect of CYP3A4*22, CYP3A5*3 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients.","authors":"Abdel-Hameed Im Ebid, Dina A Ismail, Neama M Lotfy, Mohamed A Mahmoud, Magdy El-Sharkawy","doi":"10.1097/FPC.0000000000000516","DOIUrl":null,"url":null,"abstract":"Objective: This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.Methods: One hundred thirty renal transplant patients placed on either tacrolimus or cyclosporine were recruited, where the effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on their dose requirements were studied at days 14, 30, and 90 post-transplantations.Results: The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was significantly lower in the fast metabolizers group ( CYP3A5*1/POR*28(CT/TT ) carriers) than in the poor metabolizers group ( CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) ( P = 0.001, <0.001, and 0.003, respectively). Meanwhile, there was no significant effect of this gene combination on cyclosporine C0/D.Conclusion: Combining the CYP3A5*3, POR*28 , and CYP3A4*22 genotypes can have a significant effect on early tacrolimus dose requirements determination and adjustments. However, it does not have such influence on cyclosporine dose requirements.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000516","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/4 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.

Methods: One hundred thirty renal transplant patients placed on either tacrolimus or cyclosporine were recruited, where the effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on their dose requirements were studied at days 14, 30, and 90 post-transplantations.

Results: The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was significantly lower in the fast metabolizers group ( CYP3A5*1/POR*28(CT/TT ) carriers) than in the poor metabolizers group ( CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) ( P = 0.001, <0.001, and 0.003, respectively). Meanwhile, there was no significant effect of this gene combination on cyclosporine C0/D.

Conclusion: Combining the CYP3A5*3, POR*28 , and CYP3A4*22 genotypes can have a significant effect on early tacrolimus dose requirements determination and adjustments. However, it does not have such influence on cyclosporine dose requirements.

查看原文本刊更多论文

CYP3A4*22、CYP3A5*3和POR*28基因多态性对早期肾移植患者钙调磷酸酶抑制剂剂量需求的影响

目的:本研究旨在探讨CYP3A5*3、CYP3A4*22和POR*28基因多态性对他克莫司和环孢素剂量需求的联合影响。方法:招募130例接受他克莫司或环孢素治疗的肾移植患者，在移植后第14、30和90天研究CYP3A5*3、CYP3A4*22和POR*28基因多态性对其剂量需求的影响。结果:研究人群中POR*28等位基因频率为29.61%。研究期间(14、30、90天)，快速代谢组(CYP3A5*1/POR*28(CT/TT)携带者)的他克莫司剂量调整谷浓度比(C0/D)显著低于代谢不良组(CYP3A5*3/*3/CYP3A4*22) (P = 0.001)。结论:结合CYP3A5*3、POR*28、CYP3A4*22基因型对早期他克莫司剂量需求的确定和调整有显著影响。然而，它对环孢素的剂量要求没有这样的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.