Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients
Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphi...
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| Veröffentlicht in: | Clinica chimica acta 2012-12, Vol.414, p.120-124 |
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| creator | Hirano, Kumi Naito, Takafumi Mino, Yasuaki Takayama, Tatsuya Ozono, Seiichiro Kawakami, Junichi |
| description | Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism.
The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots.
No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3μg/l and CYP3A5*1/*3 genotype.
This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels.
► We evaluated the cross-reactivity in tacrolimus CLIA in kidney transplantation. ► CYP3A5*3 affected the metabolic pathway of tacrolimus and its blood level. ► Blood tacrolimus level measured by CLIA was 35% higher than that by LC–MS/MS. ► A higher cross-reactivity was found in patients with a tacrolimus level of |
| doi_str_mv | 10.1016/j.cca.2012.07.018 |
| format | Article |
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The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots.
No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3μg/l and CYP3A5*1/*3 genotype.
This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels.
► We evaluated the cross-reactivity in tacrolimus CLIA in kidney transplantation. ► CYP3A5*3 affected the metabolic pathway of tacrolimus and its blood level. ► Blood tacrolimus level measured by CLIA was 35% higher than that by LC–MS/MS. ► A higher cross-reactivity was found in patients with a tacrolimus level of <3μg/l. ► A higher cross-reactivity was found in patients with the CYP3A5*1 allele.</description><identifier>ISSN: 0009-8981</identifier><identifier>EISSN: 1873-3492</identifier><identifier>DOI: 10.1016/j.cca.2012.07.018</identifier><identifier>PMID: 22889968</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Chemiluminescent immunoassay ; Cross Reactions ; Cross-reactivity ; CYP3A5 ; Cytochrome P-450 CYP3A - genetics ; Female ; Genotype ; Humans ; Immunoassay ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - chemistry ; Immunosuppressive Agents - metabolism ; Kidney Transplantation ; Luminescent Measurements ; Male ; Middle Aged ; Polymorphism, Genetic - genetics ; Tacrolimus ; Tacrolimus - blood ; Tacrolimus - chemistry ; Tacrolimus - metabolism</subject><ispartof>Clinica chimica acta, 2012-12, Vol.414, p.120-124</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-177407c509aeeb9371699b2f78de76f3d5ee4d4741ea7f110b0d9c949be332d53</citedby><cites>FETCH-LOGICAL-c419t-177407c509aeeb9371699b2f78de76f3d5ee4d4741ea7f110b0d9c949be332d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0009898112003798$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22889968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirano, Kumi</creatorcontrib><creatorcontrib>Naito, Takafumi</creatorcontrib><creatorcontrib>Mino, Yasuaki</creatorcontrib><creatorcontrib>Takayama, Tatsuya</creatorcontrib><creatorcontrib>Ozono, Seiichiro</creatorcontrib><creatorcontrib>Kawakami, Junichi</creatorcontrib><title>Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients</title><title>Clinica chimica acta</title><addtitle>Clin Chim Acta</addtitle><description>Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism.
The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots.
No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3μg/l and CYP3A5*1/*3 genotype.
This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels.
► We evaluated the cross-reactivity in tacrolimus CLIA in kidney transplantation. ► CYP3A5*3 affected the metabolic pathway of tacrolimus and its blood level. ► Blood tacrolimus level measured by CLIA was 35% higher than that by LC–MS/MS. ► A higher cross-reactivity was found in patients with a tacrolimus level of <3μg/l. ► A higher cross-reactivity was found in patients with the CYP3A5*1 allele.</description><subject>Adult</subject><subject>Chemiluminescent immunoassay</subject><subject>Cross Reactions</subject><subject>Cross-reactivity</subject><subject>CYP3A5</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - chemistry</subject><subject>Immunosuppressive Agents - metabolism</subject><subject>Kidney Transplantation</subject><subject>Luminescent Measurements</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Tacrolimus</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - chemistry</subject><subject>Tacrolimus - metabolism</subject><issn>0009-8981</issn><issn>1873-3492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1vFDEQhi0ESi4hP4AGuaTZxV-3XosqOgWIFAmKpKCyvPYs8bFeL7Y30vX8cJxcSEk1mtEzr2YehN5R0lJCu4_71lrTMkJZS2RLaP8KbWgvecOFYq_RhhCiml719BSd5byvrSAdPUGnjPW9Ul2_QX-uw2JswXHEux_f-eUW_4QZird4idMhxLTc-xxwnLFNMecmQaX9gy8H7GdcTJ1OPqwZ23sIflqDnyFbmAv2IaxzNDmbJ_SXdzMccElmzstkKpDA-sVXNL9Fb0YzZbh4rufo7vPV7e5rc_Pty_Xu8qaxgqrSUCkFkXZLlAEYFJe0U2pgo-wdyG7kbgsgnJCCgpEjpWQgTlkl1ACcM7fl5-jDMXdJ8fcKuejg67FTPQfimjVljPBOSNJVlB7Rp7cTjHpJPph00JToR_l6r6t8_ShfE6mr_Lrz_jl-HQK4l41_tivw6QhAffLBQ9LZVgEWnK8yinbR_yf-LzN6l8o</recordid><startdate>20121224</startdate><enddate>20121224</enddate><creator>Hirano, Kumi</creator><creator>Naito, Takafumi</creator><creator>Mino, Yasuaki</creator><creator>Takayama, Tatsuya</creator><creator>Ozono, Seiichiro</creator><creator>Kawakami, Junichi</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20121224</creationdate><title>Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients</title><author>Hirano, Kumi ; Naito, Takafumi ; Mino, Yasuaki ; Takayama, Tatsuya ; Ozono, Seiichiro ; Kawakami, Junichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-177407c509aeeb9371699b2f78de76f3d5ee4d4741ea7f110b0d9c949be332d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Chemiluminescent immunoassay</topic><topic>Cross Reactions</topic><topic>Cross-reactivity</topic><topic>CYP3A5</topic><topic>Cytochrome P-450 CYP3A - genetics</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - chemistry</topic><topic>Immunosuppressive Agents - metabolism</topic><topic>Kidney Transplantation</topic><topic>Luminescent Measurements</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Tacrolimus</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - chemistry</topic><topic>Tacrolimus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirano, Kumi</creatorcontrib><creatorcontrib>Naito, Takafumi</creatorcontrib><creatorcontrib>Mino, Yasuaki</creatorcontrib><creatorcontrib>Takayama, Tatsuya</creatorcontrib><creatorcontrib>Ozono, Seiichiro</creatorcontrib><creatorcontrib>Kawakami, Junichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinica chimica acta</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirano, Kumi</au><au>Naito, Takafumi</au><au>Mino, Yasuaki</au><au>Takayama, Tatsuya</au><au>Ozono, Seiichiro</au><au>Kawakami, Junichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients</atitle><jtitle>Clinica chimica acta</jtitle><addtitle>Clin Chim Acta</addtitle><date>2012-12-24</date><risdate>2012</risdate><volume>414</volume><spage>120</spage><epage>124</epage><pages>120-124</pages><issn>0009-8981</issn><eissn>1873-3492</eissn><abstract>Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism.
The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots.
No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3μg/l and CYP3A5*1/*3 genotype.
This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels.
► We evaluated the cross-reactivity in tacrolimus CLIA in kidney transplantation. ► CYP3A5*3 affected the metabolic pathway of tacrolimus and its blood level. ► Blood tacrolimus level measured by CLIA was 35% higher than that by LC–MS/MS. ► A higher cross-reactivity was found in patients with a tacrolimus level of <3μg/l. ► A higher cross-reactivity was found in patients with the CYP3A5*1 allele.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22889968</pmid><doi>10.1016/j.cca.2012.07.018</doi><tpages>5</tpages></addata></record> |
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| subjects | Adult Chemiluminescent immunoassay Cross Reactions Cross-reactivity CYP3A5 Cytochrome P-450 CYP3A - genetics Female Genotype Humans Immunoassay Immunosuppressive Agents - blood Immunosuppressive Agents - chemistry Immunosuppressive Agents - metabolism Kidney Transplantation Luminescent Measurements Male Middle Aged Polymorphism, Genetic - genetics Tacrolimus Tacrolimus - blood Tacrolimus - chemistry Tacrolimus - metabolism |
| title | Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients |
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