Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients
Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA...
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description | Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites. |
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Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1111/j.1745-7254.2006.00428.x</identifier><identifier>PMID: 17049128</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Adult ; Asian Continental Ancestry Group ; China ; cyclosporine ; Cyclosporine - metabolism ; CYP3A5 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - genetics ; DNA Primers ; Female ; genetic polymorphism ; Genotype ; Humans ; Kidney Transplantation ; Male ; metabolic ratio ; Middle Aged ; Polymorphism, Genetic ; renal transplant patients ; 新陈代谢 ; 环孢霉素 ; 遗传多态性</subject><ispartof>Acta pharmacologica Sinica, 2006-11, Vol.27 (11), p.1504-1508</ispartof><rights>Copyright Nature Publishing Group Nov 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5028-9be33e15dd077b5c8672019d7f3771b30acb6c6869ce7cc11b217d6a7c8b79503</citedby><cites>FETCH-LOGICAL-c5028-9be33e15dd077b5c8672019d7f3771b30acb6c6869ce7cc11b217d6a7c8b79503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1745-7254.2006.00428.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1745-7254.2006.00428.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17049128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHU, Xiao‐man</creatorcontrib><creatorcontrib>HAO, Hai‐ping</creatorcontrib><creatorcontrib>WANG, Guang‐ji</creatorcontrib><creatorcontrib>GUO, Lian‐qing</creatorcontrib><creatorcontrib>MIN, Pei‐qing</creatorcontrib><title>Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.</description><subject>Adult</subject><subject>Asian Continental Ancestry Group</subject><subject>China</subject><subject>cyclosporine</subject><subject>Cyclosporine - metabolism</subject><subject>CYP3A5</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>DNA Primers</subject><subject>Female</subject><subject>genetic polymorphism</subject><subject>Genotype</subject><subject>Humans</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>metabolic ratio</subject><subject>Middle Aged</subject><subject>Polymorphism, Genetic</subject><subject>renal transplant patients</subject><subject>新陈代谢</subject><subject>环孢霉素</subject><subject>遗传多态性</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks2L1DAYh4so7of-CxI8eJuaj7ZJDh6GYXUXFlxQD55Cmr6dyZgm3aTFHfCP33RnUPCiuSTkfd4feXlSFIjgkuT1fl8SXtUrTuuqpBg3JcYVFeXDs-L8d-F5PjecrCos2FlxkdIeY0YZkS-LM8JxJQkV58WvG9-7GbwBFHq0-X7H1jXagofJGjQGdxhCHHc2DSh4ZA7GhTSGaD2gNRpg0m1wS1H7DoGzg_V6spm0Hm12mUqAInjt0BS1T6PTfsoXxo4W_JReFS967RK8Pu2XxbePV18316vbz59uNuvblakxFSvZAmNA6q7DnLe1EQ2nmMiO94xz0jKsTduYRjTSADeGkJYS3jWaG9FyWWN2Wbw75o4x3M-QJjXYZMDl50CYk2qE5JJg-U-QyLpiVCzg27_AfZhjHjQpShjGnFZ1hsQRMjGkFKFXY7SDjgdFsFo8qr1adKlFl1o8qieP6iG3vjnlz-0A3Z_Gk7gMfDgCP62Dw38Hq_Xd9Zfqqf80gNkFv723fqtabX70OU3lT4JZLTl7BLF3t7s</recordid><startdate>200611</startdate><enddate>200611</enddate><creator>CHU, Xiao‐man</creator><creator>HAO, Hai‐ping</creator><creator>WANG, Guang‐ji</creator><creator>GUO, Lian‐qing</creator><creator>MIN, Pei‐qing</creator><general>Blackwell Publishing Asia</general><general>Nature Publishing Group</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</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>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200611</creationdate><title>Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients</title><author>CHU, Xiao‐man ; HAO, Hai‐ping ; WANG, Guang‐ji ; GUO, Lian‐qing ; MIN, Pei‐qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5028-9be33e15dd077b5c8672019d7f3771b30acb6c6869ce7cc11b217d6a7c8b79503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Asian Continental Ancestry Group</topic><topic>China</topic><topic>cyclosporine</topic><topic>Cyclosporine - metabolism</topic><topic>CYP3A5</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>DNA Primers</topic><topic>Female</topic><topic>genetic polymorphism</topic><topic>Genotype</topic><topic>Humans</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>metabolic ratio</topic><topic>Middle Aged</topic><topic>Polymorphism, Genetic</topic><topic>renal transplant patients</topic><topic>新陈代谢</topic><topic>环孢霉素</topic><topic>遗传多态性</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHU, Xiao‐man</creatorcontrib><creatorcontrib>HAO, Hai‐ping</creatorcontrib><creatorcontrib>WANG, Guang‐ji</creatorcontrib><creatorcontrib>GUO, Lian‐qing</creatorcontrib><creatorcontrib>MIN, Pei‐qing</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHU, Xiao‐man</au><au>HAO, Hai‐ping</au><au>WANG, Guang‐ji</au><au>GUO, Lian‐qing</au><au>MIN, Pei‐qing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients</atitle><jtitle>Acta pharmacologica Sinica</jtitle><addtitle>Acta Pharmacologica Sinica</addtitle><date>2006-11</date><risdate>2006</risdate><volume>27</volume><issue>11</issue><spage>1504</spage><epage>1508</epage><pages>1504-1508</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>17049128</pmid><doi>10.1111/j.1745-7254.2006.00428.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Asian Continental Ancestry Group China cyclosporine Cyclosporine - metabolism CYP3A5 Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics DNA Primers Female genetic polymorphism Genotype Humans Kidney Transplantation Male metabolic ratio Middle Aged Polymorphism, Genetic renal transplant patients 新陈代谢 环孢霉素 遗传多态性 |
title | Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients |
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