Abdel-Hameed Im Ebid, Dina A Ismail, Neama M Lotfy, Mohamed A Mahmoud, Magdy El-Sharkawy
{"title":"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","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":"<p><strong>Objective: </strong>This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"43-52"},"PeriodicalIF":1.7000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"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\":\"<p><strong>Objective: </strong>This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":19763,\"journal\":{\"name\":\"Pharmacogenetics and genomics\",\"volume\":\" \",\"pages\":\"43-52\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenetics and genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FPC.0000000000000516\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenetics and genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000516","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/4 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Effect of CYP3A4*22, CYP3A5*3 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients.
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.
期刊介绍：
Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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