Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation
Tacrolimus is a widely used immunosuppressant in organ transplantation, but it is characterized by a narrow therapeutic index and high interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with tacrolim...
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| Veröffentlicht in: | Transplantation 2006-01, Vol.81 (1), p.46-51 |
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| creator | Yu, Songfeng Wu, Lihua Jin, Jing Yan, Sheng Jiang, Guoping Xie, Haiyang Zheng, Shusen |
| description | Tacrolimus is a widely used immunosuppressant in organ transplantation, but it is characterized by a narrow therapeutic index and high interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. The objective of this study was to evaluate the contribution of polymorphisms of the donor and recipient CYP3A5 gene on tacrolimus disposition in liver transplantation.
Fifty-three liver transplant recipients treated with tacrolimus were enrolled in this study. Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2 weeks, and 1 month after transplantation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 gene.
The concentration/dose (C/D) ratios in patients with *1/*1(*1/*3) genotype donor were significantly lower than in patients with *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1 week posttransplantation. Combination analysis showed that such significance still existed between CYP3A5 expressor group and nonexpressor group for both donor and recipient genotype. Also differences of C/D ratio between CYP3A5 expressor and nonexpressor donors in nonexpressor recipients were larger than those between recipients in nonexpressor donors.
The large interindividual variation of tacrolimus dose requirement is influenced by the metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to contribute more to such variation than the recipient. A larger population and further studies are needed to explore the exact mechanisms for tacrolimus pharmacokinetics. |
| doi_str_mv | 10.1097/01.tp.0000188118.34633.bf |
| format | Article |
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Fifty-three liver transplant recipients treated with tacrolimus were enrolled in this study. Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2 weeks, and 1 month after transplantation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 gene.
The concentration/dose (C/D) ratios in patients with *1/*1(*1/*3) genotype donor were significantly lower than in patients with *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1 week posttransplantation. Combination analysis showed that such significance still existed between CYP3A5 expressor group and nonexpressor group for both donor and recipient genotype. Also differences of C/D ratio between CYP3A5 expressor and nonexpressor donors in nonexpressor recipients were larger than those between recipients in nonexpressor donors.
The large interindividual variation of tacrolimus dose requirement is influenced by the metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to contribute more to such variation than the recipient. A larger population and further studies are needed to explore the exact mechanisms for tacrolimus pharmacokinetics.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/01.tp.0000188118.34633.bf</identifier><identifier>PMID: 16421475</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Adult ; Aged ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Biological and medical sciences ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - genetics ; Dose-Response Relationship, Drug ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genotype ; Humans ; Liver Transplantation - immunology ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Polymorphism, Genetic - genetics ; Retrospective Studies ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tacrolimus - administration & dosage ; Tacrolimus - pharmacokinetics ; Tissue Donors ; Tissue, organ and graft immunology</subject><ispartof>Transplantation, 2006-01, Vol.81 (1), p.46-51</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-98ae9e152276b2e8178b07175704bbfde20aaa3fa84c99a2ce40bdd75eb87c2e3</citedby><cites>FETCH-LOGICAL-c493t-98ae9e152276b2e8178b07175704bbfde20aaa3fa84c99a2ce40bdd75eb87c2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17449984$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16421475$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Songfeng</creatorcontrib><creatorcontrib>Wu, Lihua</creatorcontrib><creatorcontrib>Jin, Jing</creatorcontrib><creatorcontrib>Yan, Sheng</creatorcontrib><creatorcontrib>Jiang, Guoping</creatorcontrib><creatorcontrib>Xie, Haiyang</creatorcontrib><creatorcontrib>Zheng, Shusen</creatorcontrib><title>Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Tacrolimus is a widely used immunosuppressant in organ transplantation, but it is characterized by a narrow therapeutic index and high interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. The objective of this study was to evaluate the contribution of polymorphisms of the donor and recipient CYP3A5 gene on tacrolimus disposition in liver transplantation.
Fifty-three liver transplant recipients treated with tacrolimus were enrolled in this study. Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2 weeks, and 1 month after transplantation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 gene.
The concentration/dose (C/D) ratios in patients with *1/*1(*1/*3) genotype donor were significantly lower than in patients with *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1 week posttransplantation. Combination analysis showed that such significance still existed between CYP3A5 expressor group and nonexpressor group for both donor and recipient genotype. Also differences of C/D ratio between CYP3A5 expressor and nonexpressor donors in nonexpressor recipients were larger than those between recipients in nonexpressor donors.
The large interindividual variation of tacrolimus dose requirement is influenced by the metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to contribute more to such variation than the recipient. A larger population and further studies are needed to explore the exact mechanisms for tacrolimus pharmacokinetics.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genotype</subject><subject>Humans</subject><subject>Liver Transplantation - immunology</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Retrospective Studies</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>Tissue Donors</subject><subject>Tissue, organ and graft immunology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi0EotvCKyBzgFuCHTsZ51itCq1UCQ5w4GQ5zoQ1SuzUdir1DXhsvHSlPTKXOczvm38fIe85qznr4RPjdV5rVoIrxbmqheyEqIfpBdnxVsiqY4q9JDvGJK-4EHBBLlP6XfhWALwmF7yTDZfQ7sifOz_NG3qLNEx0__ObuG7pL_RI1zA_LSGuB5eWdCyOwYdIo8kHjDQfjKcRrVsd-kxzoNnYGGa3bIk6P7pHN25mLqKEhXvYXMTlSDpPZ_d47BCNT-tsfDbZBf-GvJrMnPDtKV-RH59vvu9vq_uvX-721_eVlb3IVa8M9sjbpoFuaFBxUAMDDi0wOQzTiA0zxojJKGn73jQWJRvGEVocFNgGxRX5-Nx3jeFhw5T14pLFuSyCYUsaWAfQdu1_QQ4SGgaygP0zWO5PKeKk1-gWE580Z_rol2Zc51Wf_dL__NLDVLTvTkO2YcHxrDwZVIAPJ8Aka-apPM26dOZAyr5XUvwFtL6ipQ</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>Yu, Songfeng</creator><creator>Wu, Lihua</creator><creator>Jin, Jing</creator><creator>Yan, Sheng</creator><creator>Jiang, Guoping</creator><creator>Xie, Haiyang</creator><creator>Zheng, Shusen</creator><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060115</creationdate><title>Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation</title><author>Yu, Songfeng ; Wu, Lihua ; Jin, Jing ; Yan, Sheng ; Jiang, Guoping ; Xie, Haiyang ; Zheng, Shusen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-98ae9e152276b2e8178b07175704bbfde20aaa3fa84c99a2ce40bdd75eb87c2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibacterial agents</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Genotype</topic><topic>Humans</topic><topic>Liver Transplantation - immunology</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Retrospective Studies</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>Tissue Donors</topic><topic>Tissue, organ and graft immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Songfeng</creatorcontrib><creatorcontrib>Wu, Lihua</creatorcontrib><creatorcontrib>Jin, Jing</creatorcontrib><creatorcontrib>Yan, Sheng</creatorcontrib><creatorcontrib>Jiang, Guoping</creatorcontrib><creatorcontrib>Xie, Haiyang</creatorcontrib><creatorcontrib>Zheng, Shusen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Songfeng</au><au>Wu, Lihua</au><au>Jin, Jing</au><au>Yan, Sheng</au><au>Jiang, Guoping</au><au>Xie, Haiyang</au><au>Zheng, Shusen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2006-01-15</date><risdate>2006</risdate><volume>81</volume><issue>1</issue><spage>46</spage><epage>51</epage><pages>46-51</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Tacrolimus is a widely used immunosuppressant in organ transplantation, but it is characterized by a narrow therapeutic index and high interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. The objective of this study was to evaluate the contribution of polymorphisms of the donor and recipient CYP3A5 gene on tacrolimus disposition in liver transplantation.
Fifty-three liver transplant recipients treated with tacrolimus were enrolled in this study. Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2 weeks, and 1 month after transplantation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 gene.
The concentration/dose (C/D) ratios in patients with *1/*1(*1/*3) genotype donor were significantly lower than in patients with *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1 week posttransplantation. Combination analysis showed that such significance still existed between CYP3A5 expressor group and nonexpressor group for both donor and recipient genotype. Also differences of C/D ratio between CYP3A5 expressor and nonexpressor donors in nonexpressor recipients were larger than those between recipients in nonexpressor donors.
The large interindividual variation of tacrolimus dose requirement is influenced by the metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to contribute more to such variation than the recipient. A larger population and further studies are needed to explore the exact mechanisms for tacrolimus pharmacokinetics.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>16421475</pmid><doi>10.1097/01.tp.0000188118.34633.bf</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 2006-01, Vol.81 (1), p.46-51 |
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| subjects | Adult Aged Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Biological and medical sciences Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics Dose-Response Relationship, Drug Fundamental and applied biological sciences. Psychology Fundamental immunology Genotype Humans Liver Transplantation - immunology Medical sciences Middle Aged Pharmacology. Drug treatments Polymorphism, Genetic - genetics Retrospective Studies Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tacrolimus - administration & dosage Tacrolimus - pharmacokinetics Tissue Donors Tissue, organ and graft immunology |
| title | Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation |
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