Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients
Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of tr...
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| description | Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs. |
| doi_str_mv | 10.1371/journal.pgen.1005910 |
| format | Article |
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A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1005910</identifier><identifier>PMID: 27010727</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Androstanes - metabolism ; Biology and Life Sciences ; Care and treatment ; Complications and side effects ; Cytochrome P-450 CYP2B6 - genetics ; Drug abuse ; Engineering and Technology ; Extracellular Matrix Proteins - genetics ; Female ; Genetic aspects ; Genome-wide association studies ; Genome-Wide Association Study ; Haplotypes - genetics ; Health aspects ; Heroin ; Heroin - metabolism ; Heroin - toxicity ; Heroin Dependence - genetics ; Heroin Dependence - metabolism ; Heroin Dependence - pathology ; Humans ; Male ; Medical research ; Medicine and Health Sciences ; Metabolites ; Methadone ; Methadone - administration & dosage ; Methadone - metabolism ; Middle Aged ; Observations ; Opiate Substitution Treatment ; Pharmacogenetics ; Pharmacogenomics ; Plasma ; Polymorphism, Single Nucleotide ; Research and Analysis Methods ; Single nucleotide polymorphisms ; Stereoisomerism</subject><ispartof>PLoS genetics, 2016-03, Vol.12 (3), p.e1005910-e1005910</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: enantiomers in Heroin-Dependent Patients. PLoS Genet 12(3): e1005910. doi:10.1371/journal.pgen.1005910</rights><rights>2016 Yang et al 2016 Yang et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: enantiomers in Heroin-Dependent Patients. PLoS Genet 12(3): e1005910. doi:10.1371/journal.pgen.1005910</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c759t-36e62fa4424568ba54e6901f2d00261d50d9f75666c240fddbe0744c562a55cb3</citedby><cites>FETCH-LOGICAL-c759t-36e62fa4424568ba54e6901f2d00261d50d9f75666c240fddbe0744c562a55cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806848/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806848/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27010727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Yang, Hsin-Chou</creatorcontrib><creatorcontrib>Chu, Shih-Kai</creatorcontrib><creatorcontrib>Huang, Chieh-Liang</creatorcontrib><creatorcontrib>Kuo, Hsiang-Wei</creatorcontrib><creatorcontrib>Wang, Sheng-Chang</creatorcontrib><creatorcontrib>Liu, Sheng-Wen</creatorcontrib><creatorcontrib>Ho, Ing-Kang</creatorcontrib><creatorcontrib>Liu, Yu-Li</creatorcontrib><title>Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.</description><subject>Adult</subject><subject>Androstanes - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Complications and side effects</subject><subject>Cytochrome P-450 CYP2B6 - genetics</subject><subject>Drug abuse</subject><subject>Engineering and Technology</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Haplotypes - genetics</subject><subject>Health aspects</subject><subject>Heroin</subject><subject>Heroin - metabolism</subject><subject>Heroin - toxicity</subject><subject>Heroin Dependence - genetics</subject><subject>Heroin Dependence - metabolism</subject><subject>Heroin Dependence - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metabolites</subject><subject>Methadone</subject><subject>Methadone - administration & dosage</subject><subject>Methadone - metabolism</subject><subject>Middle Aged</subject><subject>Observations</subject><subject>Opiate Substitution Treatment</subject><subject>Pharmacogenetics</subject><subject>Pharmacogenomics</subject><subject>Plasma</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Research and Analysis Methods</subject><subject>Single nucleotide polymorphisms</subject><subject>Stereoisomerism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk11v0zAUhiMEYmPwDxBYQkIgLcVO4ji-QRoFukr7qNYB4spy45PWU2KX2AH2y7nFabupRbsYihRbx895fT58oug5wQOSMvLuynatkfVgOQczIBhTTvCDaJ9QmsYsw9nDrf1e9MS5K4xTWnD2ONpLGCaYJWw_-jMCYxuIv2kFaLKQbSNLO-9tukRT36lrZA06Bb-QyhpAp1IbD0aaEtBlC9I3YDwaq_DXlQaHpmcT1DrCSIETzpE0Cp12tdfLGtCxXNbWXy8DFkSH3yfJh_wQTSfnZ-RwRY6mI3KCjpyzpZYeFPql_QJNaukaiYY2XGp8K722JihUW2FdxCv_adyHFs4baB3SBh1Da7WJP8ISTB8jmgTvsLqn0aNK1g6ebdaD6MvnT5fD4_jkfDQeHp3EJaPcx2kOeVLJLEsymhczSTPIOSZVojBOcqIoVrxiNM_zMslwpdQMMMuykuaJpLScpQfRy7VuyNyJTc-cIKwgKSc8o4EYrwll5ZVYtrqR7bWwUouVwbZzIVuvyxqEmvE0YVDyKoSkCjWTKpnlNJmlwIsCF0Hr_ea2btaAWper3hHdPTF6Ieb2p8gKnBdZL_BmI9DaHx04LxrtSqhracB2q7gZz1mSpvdAWY4LTlmf4qt_0LsLsaHmMuSqTWVDiGUvKo4yxmka6txTgzuo8CkITza8hUoH-47D2x2HwHj47eeyc06Mpxf_wZ7dnz3_usu-3mIXIGu_cLbuVi95F8zWYNla51qobntHsOjH_qZyoh97sRn74PZiu--3Tjdznv4FseZSLA</recordid><startdate>20160324</startdate><enddate>20160324</enddate><creator>Yang, Hsin-Chou</creator><creator>Chu, Shih-Kai</creator><creator>Huang, Chieh-Liang</creator><creator>Kuo, Hsiang-Wei</creator><creator>Wang, Sheng-Chang</creator><creator>Liu, Sheng-Wen</creator><creator>Ho, Ing-Kang</creator><creator>Liu, Yu-Li</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</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>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160324</creationdate><title>Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients</title><author>Yang, Hsin-Chou ; Chu, Shih-Kai ; Huang, Chieh-Liang ; Kuo, Hsiang-Wei ; Wang, Sheng-Chang ; Liu, Sheng-Wen ; Ho, Ing-Kang ; Liu, Yu-Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c759t-36e62fa4424568ba54e6901f2d00261d50d9f75666c240fddbe0744c562a55cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Androstanes - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Care and treatment</topic><topic>Complications and side effects</topic><topic>Cytochrome P-450 CYP2B6 - genetics</topic><topic>Drug abuse</topic><topic>Engineering and Technology</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Haplotypes - genetics</topic><topic>Health aspects</topic><topic>Heroin</topic><topic>Heroin - metabolism</topic><topic>Heroin - toxicity</topic><topic>Heroin Dependence - genetics</topic><topic>Heroin Dependence - metabolism</topic><topic>Heroin Dependence - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Metabolites</topic><topic>Methadone</topic><topic>Methadone - administration & dosage</topic><topic>Methadone - metabolism</topic><topic>Middle Aged</topic><topic>Observations</topic><topic>Opiate Substitution Treatment</topic><topic>Pharmacogenetics</topic><topic>Pharmacogenomics</topic><topic>Plasma</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Research and Analysis Methods</topic><topic>Single nucleotide polymorphisms</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Hsin-Chou</creatorcontrib><creatorcontrib>Chu, Shih-Kai</creatorcontrib><creatorcontrib>Huang, Chieh-Liang</creatorcontrib><creatorcontrib>Kuo, Hsiang-Wei</creatorcontrib><creatorcontrib>Wang, Sheng-Chang</creatorcontrib><creatorcontrib>Liu, Sheng-Wen</creatorcontrib><creatorcontrib>Ho, Ing-Kang</creatorcontrib><creatorcontrib>Liu, Yu-Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors 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>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content 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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Hsin-Chou</au><au>Chu, Shih-Kai</au><au>Huang, Chieh-Liang</au><au>Kuo, Hsiang-Wei</au><au>Wang, Sheng-Chang</au><au>Liu, Sheng-Wen</au><au>Ho, Ing-Kang</au><au>Liu, Yu-Li</au><au>Barsh, Gregory S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2016-03-24</date><risdate>2016</risdate><volume>12</volume><issue>3</issue><spage>e1005910</spage><epage>e1005910</epage><pages>e1005910-e1005910</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27010727</pmid><doi>10.1371/journal.pgen.1005910</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1781391945 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Adult Androstanes - metabolism Biology and Life Sciences Care and treatment Complications and side effects Cytochrome P-450 CYP2B6 - genetics Drug abuse Engineering and Technology Extracellular Matrix Proteins - genetics Female Genetic aspects Genome-wide association studies Genome-Wide Association Study Haplotypes - genetics Health aspects Heroin Heroin - metabolism Heroin - toxicity Heroin Dependence - genetics Heroin Dependence - metabolism Heroin Dependence - pathology Humans Male Medical research Medicine and Health Sciences Metabolites Methadone Methadone - administration & dosage Methadone - metabolism Middle Aged Observations Opiate Substitution Treatment Pharmacogenetics Pharmacogenomics Plasma Polymorphism, Single Nucleotide Research and Analysis Methods Single nucleotide polymorphisms Stereoisomerism |
| title | Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T02%3A39%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-Wide%20Pharmacogenomic%20Study%20on%20Methadone%20Maintenance%20Treatment%20Identifies%20SNP%20rs17180299%20and%20Multiple%20Haplotypes%20on%20CYP2B6,%20SPON1,%20and%20GSG1L%20Associated%20with%20Plasma%20Concentrations%20of%20Methadone%20R-%20and%20S-enantiomers%20in%20Heroin-Dependent%20Patients&rft.jtitle=PLoS%20genetics&rft.au=Yang,%20Hsin-Chou&rft.date=2016-03-24&rft.volume=12&rft.issue=3&rft.spage=e1005910&rft.epage=e1005910&rft.pages=e1005910-e1005910&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1005910&rft_dat=%3Cgale_plos_%3EA479537565%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781391945&rft_id=info:pmid/27010727&rft_galeid=A479537565&rft_doaj_id=oai_doaj_org_article_db9327ec9ffa4d8dbad2b652b3e98808&rfr_iscdi=true |