The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients
This study aimed to investigate the effect of and mechanism involved in the SNP on cyclosporine metabolism and outcomes of liver transplantation (LT). The genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of...
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| Veröffentlicht in: | Pharmacogenomics 2019-04, Vol.20 (6), p.447-456 |
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| creator | Sun, Bo Gao, Junwei Shi, Weifeng Guo, Yankun Fan, Junwei Zhang, Jigang Li, Xiaoyu Liu, Gaolin |
| description | This study aimed to investigate the effect of and mechanism involved in the
SNP on cyclosporine metabolism and outcomes of liver transplantation (LT).
The
genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of rs2275913 was evaluated by luciferase assay. Furthermore, L02 cells were treated with IL-17 recombinant protein or/and pregnane X receptor (PXR) knockdown lentiviruses, then the expression of PXR, CYP3A4, CYP3A5 and IL-17R were detected by PCR and western blotting.
The significant distribution difference at
locus G-197A was confirmed between patients with and without rejection (p = 0.035). Patients with acute rejection showed higher IL-17 level than those without rejection. Cyclosporine concentration was associated with the different
genotype (p < 0.05). Luciferase assay revealed that 197G genotype had higher luciferase activity than that in 197A genotype (p = 0.009). Furthermore, IL-17 recombinant protein remarkably promoted the expressions of PXR, CYP3A4 and CYP3A5 (p < 0.01), but not IL-17R. PXR knockdown significantly inhibited the mRNA levels of CYP3A4 and CYP3A5 but not IL-17R (p < 0.01), while IL-17 recombinant protein had no influence on the expressions of CYP3A4 and CYP3A5 when PXR was downregulated.
This study revealed the possible association of IL-17 G-197A with cyclosporine metabolism and transplant rejection after LT, which might be partly related to the upregulations of CYP3A4/5 dependent on PXR. |
| doi_str_mv | 10.2217/pgs-2018-0198 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2185874186</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2185874186</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-d112869cdea564512324c4a6d24108880b434fa765dd274d21e274bcff3063d73</originalsourceid><addsrcrecordid>eNp1kUFvFCEUx4nR2Np69GpIvHhBgWGAOTZNrU2a9NKeCQtvXNYZGIGx2Y_gty6brSaaeHoQfvx5vB9C7xj9xDlTn5dvhXDKNKFs0C_QKVNCEE0Ff9nWQnLCBZMn6E0pO0o5k4K-RicdVcOgeH-Kft1vAYdYIU-wfg-RMIWvCRvUBV7StJ9TXrahzDgUbEtJLtgKHj-GusVu76ZUlpRDBDxDtZs0HVAbPa7ZxrJMNlacYQeuhhTbM3gKPyH_ferCEiDWco5ejXYq8Pa5nqGHL1f3l1_J7d31zeXFLXGdYpV4xriWg_Ngeyl6xjsunLDSt39SrTXdiE6MVsnee66E5wxa2bhx7KjsvOrO0Mdj7pLTjxVKNXMoDqbWDqS1GM50r5VgWjb0wz_oLq05tu4M50qqQUrKG0WOlMuplAyjWXKYbd4bRs3BkWmOzMGROThq_Pvn1HUzg_9D_5bSgOEIjGtdMxTX5uPAHHftRnBt4v8JfwK-w6Gu</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2276796602</pqid></control><display><type>article</type><title>The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients</title><source>MEDLINE</source><source>PubMed Central</source><creator>Sun, Bo ; Gao, Junwei ; Shi, Weifeng ; Guo, Yankun ; Fan, Junwei ; Zhang, Jigang ; Li, Xiaoyu ; Liu, Gaolin</creator><creatorcontrib>Sun, Bo ; Gao, Junwei ; Shi, Weifeng ; Guo, Yankun ; Fan, Junwei ; Zhang, Jigang ; Li, Xiaoyu ; Liu, Gaolin</creatorcontrib><description>This study aimed to investigate the effect of and mechanism involved in the
SNP on cyclosporine metabolism and outcomes of liver transplantation (LT).
The
genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of rs2275913 was evaluated by luciferase assay. Furthermore, L02 cells were treated with IL-17 recombinant protein or/and pregnane X receptor (PXR) knockdown lentiviruses, then the expression of PXR, CYP3A4, CYP3A5 and IL-17R were detected by PCR and western blotting.
The significant distribution difference at
locus G-197A was confirmed between patients with and without rejection (p = 0.035). Patients with acute rejection showed higher IL-17 level than those without rejection. Cyclosporine concentration was associated with the different
genotype (p < 0.05). Luciferase assay revealed that 197G genotype had higher luciferase activity than that in 197A genotype (p = 0.009). Furthermore, IL-17 recombinant protein remarkably promoted the expressions of PXR, CYP3A4 and CYP3A5 (p < 0.01), but not IL-17R. PXR knockdown significantly inhibited the mRNA levels of CYP3A4 and CYP3A5 but not IL-17R (p < 0.01), while IL-17 recombinant protein had no influence on the expressions of CYP3A4 and CYP3A5 when PXR was downregulated.
This study revealed the possible association of IL-17 G-197A with cyclosporine metabolism and transplant rejection after LT, which might be partly related to the upregulations of CYP3A4/5 dependent on PXR.</description><identifier>ISSN: 1462-2416</identifier><identifier>EISSN: 1744-8042</identifier><identifier>DOI: 10.2217/pgs-2018-0198</identifier><identifier>PMID: 30799725</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Adolescent ; Adult ; Aged ; cyclosporine ; Cyclosporine - metabolism ; Cyclosporins ; Cytochrome ; Cytochrome P-450 CYP3A - genetics ; Cytokines ; Deoxyribonucleic acid ; Disease ; DNA ; Down-Regulation - genetics ; Drug dosages ; Female ; Gene expression ; Gene polymorphism ; Genotype ; Graft rejection ; Graft Rejection - genetics ; Graft Rejection - metabolism ; Humans ; IL-17 ; Immunology ; Interleukin 17 ; Interleukin-17 - genetics ; Liver ; Liver transplantation ; Liver Transplantation - methods ; Liver transplants ; Male ; Metabolism ; Middle Aged ; mRNA ; Plasmids ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Pregnane X Receptor - genetics ; Proteins ; Recombinant Proteins - genetics ; RNA, Messenger - genetics ; Single-nucleotide polymorphism ; Studies ; Transplant Recipients ; Transplants & implants ; Tuberculosis ; Up-Regulation - genetics ; Western blotting ; Young Adult</subject><ispartof>Pharmacogenomics, 2019-04, Vol.20 (6), p.447-456</ispartof><rights>2019 Future Medicine Ltd</rights><rights>Copyright Future Medicine Ltd Apr 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-d112869cdea564512324c4a6d24108880b434fa765dd274d21e274bcff3063d73</citedby><cites>FETCH-LOGICAL-c371t-d112869cdea564512324c4a6d24108880b434fa765dd274d21e274bcff3063d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30799725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Bo</creatorcontrib><creatorcontrib>Gao, Junwei</creatorcontrib><creatorcontrib>Shi, Weifeng</creatorcontrib><creatorcontrib>Guo, Yankun</creatorcontrib><creatorcontrib>Fan, Junwei</creatorcontrib><creatorcontrib>Zhang, Jigang</creatorcontrib><creatorcontrib>Li, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Gaolin</creatorcontrib><title>The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients</title><title>Pharmacogenomics</title><addtitle>Pharmacogenomics</addtitle><description>This study aimed to investigate the effect of and mechanism involved in the
SNP on cyclosporine metabolism and outcomes of liver transplantation (LT).
The
genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of rs2275913 was evaluated by luciferase assay. Furthermore, L02 cells were treated with IL-17 recombinant protein or/and pregnane X receptor (PXR) knockdown lentiviruses, then the expression of PXR, CYP3A4, CYP3A5 and IL-17R were detected by PCR and western blotting.
The significant distribution difference at
locus G-197A was confirmed between patients with and without rejection (p = 0.035). Patients with acute rejection showed higher IL-17 level than those without rejection. Cyclosporine concentration was associated with the different
genotype (p < 0.05). Luciferase assay revealed that 197G genotype had higher luciferase activity than that in 197A genotype (p = 0.009). Furthermore, IL-17 recombinant protein remarkably promoted the expressions of PXR, CYP3A4 and CYP3A5 (p < 0.01), but not IL-17R. PXR knockdown significantly inhibited the mRNA levels of CYP3A4 and CYP3A5 but not IL-17R (p < 0.01), while IL-17 recombinant protein had no influence on the expressions of CYP3A4 and CYP3A5 when PXR was downregulated.
This study revealed the possible association of IL-17 G-197A with cyclosporine metabolism and transplant rejection after LT, which might be partly related to the upregulations of CYP3A4/5 dependent on PXR.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>cyclosporine</subject><subject>Cyclosporine - metabolism</subject><subject>Cyclosporins</subject><subject>Cytochrome</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>Disease</subject><subject>DNA</subject><subject>Down-Regulation - genetics</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Genotype</subject><subject>Graft rejection</subject><subject>Graft Rejection - genetics</subject><subject>Graft Rejection - metabolism</subject><subject>Humans</subject><subject>IL-17</subject><subject>Immunology</subject><subject>Interleukin 17</subject><subject>Interleukin-17 - genetics</subject><subject>Liver</subject><subject>Liver transplantation</subject><subject>Liver Transplantation - methods</subject><subject>Liver transplants</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>Plasmids</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Pregnane X Receptor - genetics</subject><subject>Proteins</subject><subject>Recombinant Proteins - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Transplant Recipients</subject><subject>Transplants & implants</subject><subject>Tuberculosis</subject><subject>Up-Regulation - genetics</subject><subject>Western blotting</subject><subject>Young Adult</subject><issn>1462-2416</issn><issn>1744-8042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFvFCEUx4nR2Np69GpIvHhBgWGAOTZNrU2a9NKeCQtvXNYZGIGx2Y_gty6brSaaeHoQfvx5vB9C7xj9xDlTn5dvhXDKNKFs0C_QKVNCEE0Ff9nWQnLCBZMn6E0pO0o5k4K-RicdVcOgeH-Kft1vAYdYIU-wfg-RMIWvCRvUBV7StJ9TXrahzDgUbEtJLtgKHj-GusVu76ZUlpRDBDxDtZs0HVAbPa7ZxrJMNlacYQeuhhTbM3gKPyH_ferCEiDWco5ejXYq8Pa5nqGHL1f3l1_J7d31zeXFLXGdYpV4xriWg_Ngeyl6xjsunLDSt39SrTXdiE6MVsnee66E5wxa2bhx7KjsvOrO0Mdj7pLTjxVKNXMoDqbWDqS1GM50r5VgWjb0wz_oLq05tu4M50qqQUrKG0WOlMuplAyjWXKYbd4bRs3BkWmOzMGROThq_Pvn1HUzg_9D_5bSgOEIjGtdMxTX5uPAHHftRnBt4v8JfwK-w6Gu</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Sun, Bo</creator><creator>Gao, Junwei</creator><creator>Shi, Weifeng</creator><creator>Guo, Yankun</creator><creator>Fan, Junwei</creator><creator>Zhang, Jigang</creator><creator>Li, Xiaoyu</creator><creator>Liu, Gaolin</creator><general>Future Medicine Ltd</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</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>EHMNL</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20190401</creationdate><title>The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients</title><author>Sun, Bo ; Gao, Junwei ; Shi, Weifeng ; Guo, Yankun ; Fan, Junwei ; Zhang, Jigang ; Li, Xiaoyu ; Liu, Gaolin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-d112869cdea564512324c4a6d24108880b434fa765dd274d21e274bcff3063d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>cyclosporine</topic><topic>Cyclosporine - metabolism</topic><topic>Cyclosporins</topic><topic>Cytochrome</topic><topic>Cytochrome P-450 CYP3A - genetics</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>Disease</topic><topic>DNA</topic><topic>Down-Regulation - genetics</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Genotype</topic><topic>Graft rejection</topic><topic>Graft Rejection - genetics</topic><topic>Graft Rejection - metabolism</topic><topic>Humans</topic><topic>IL-17</topic><topic>Immunology</topic><topic>Interleukin 17</topic><topic>Interleukin-17 - genetics</topic><topic>Liver</topic><topic>Liver transplantation</topic><topic>Liver Transplantation - methods</topic><topic>Liver transplants</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>Plasmids</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Pregnane X Receptor - genetics</topic><topic>Proteins</topic><topic>Recombinant Proteins - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><topic>Transplant Recipients</topic><topic>Transplants & implants</topic><topic>Tuberculosis</topic><topic>Up-Regulation - genetics</topic><topic>Western blotting</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Bo</creatorcontrib><creatorcontrib>Gao, Junwei</creatorcontrib><creatorcontrib>Shi, Weifeng</creatorcontrib><creatorcontrib>Guo, Yankun</creatorcontrib><creatorcontrib>Fan, Junwei</creatorcontrib><creatorcontrib>Zhang, Jigang</creatorcontrib><creatorcontrib>Li, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Gaolin</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>UK & Ireland Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Pharmacogenomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Bo</au><au>Gao, Junwei</au><au>Shi, Weifeng</au><au>Guo, Yankun</au><au>Fan, Junwei</au><au>Zhang, Jigang</au><au>Li, Xiaoyu</au><au>Liu, Gaolin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients</atitle><jtitle>Pharmacogenomics</jtitle><addtitle>Pharmacogenomics</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>20</volume><issue>6</issue><spage>447</spage><epage>456</epage><pages>447-456</pages><issn>1462-2416</issn><eissn>1744-8042</eissn><abstract>This study aimed to investigate the effect of and mechanism involved in the
SNP on cyclosporine metabolism and outcomes of liver transplantation (LT).
The
genotype, IL-17 expression, postoperative outcome and cyclosporine concentration were reviewed in 106 LT recipients. The functional relevance of rs2275913 was evaluated by luciferase assay. Furthermore, L02 cells were treated with IL-17 recombinant protein or/and pregnane X receptor (PXR) knockdown lentiviruses, then the expression of PXR, CYP3A4, CYP3A5 and IL-17R were detected by PCR and western blotting.
The significant distribution difference at
locus G-197A was confirmed between patients with and without rejection (p = 0.035). Patients with acute rejection showed higher IL-17 level than those without rejection. Cyclosporine concentration was associated with the different
genotype (p < 0.05). Luciferase assay revealed that 197G genotype had higher luciferase activity than that in 197A genotype (p = 0.009). Furthermore, IL-17 recombinant protein remarkably promoted the expressions of PXR, CYP3A4 and CYP3A5 (p < 0.01), but not IL-17R. PXR knockdown significantly inhibited the mRNA levels of CYP3A4 and CYP3A5 but not IL-17R (p < 0.01), while IL-17 recombinant protein had no influence on the expressions of CYP3A4 and CYP3A5 when PXR was downregulated.
This study revealed the possible association of IL-17 G-197A with cyclosporine metabolism and transplant rejection after LT, which might be partly related to the upregulations of CYP3A4/5 dependent on PXR.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>30799725</pmid><doi>10.2217/pgs-2018-0198</doi><tpages>10</tpages></addata></record> |
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| ispartof | Pharmacogenomics, 2019-04, Vol.20 (6), p.447-456 |
| issn | 1462-2416 1744-8042 |
| language | eng |
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| source | MEDLINE; PubMed Central |
| subjects | Adolescent Adult Aged cyclosporine Cyclosporine - metabolism Cyclosporins Cytochrome Cytochrome P-450 CYP3A - genetics Cytokines Deoxyribonucleic acid Disease DNA Down-Regulation - genetics Drug dosages Female Gene expression Gene polymorphism Genotype Graft rejection Graft Rejection - genetics Graft Rejection - metabolism Humans IL-17 Immunology Interleukin 17 Interleukin-17 - genetics Liver Liver transplantation Liver Transplantation - methods Liver transplants Male Metabolism Middle Aged mRNA Plasmids Polymorphism Polymorphism, Single Nucleotide - genetics Pregnane X Receptor - genetics Proteins Recombinant Proteins - genetics RNA, Messenger - genetics Single-nucleotide polymorphism Studies Transplant Recipients Transplants & implants Tuberculosis Up-Regulation - genetics Western blotting Young Adult |
| title | The interleukin-17 G-197A polymorphism is associated with cyclosporine metabolism and transplant rejection in liver transplant recipients |
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