Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences
Genetic variants in the OPRM1 and CYP2B6 genes, respectively coding for an opioid receptor and methadone metabolizers, have been linked to negative treatment outcomes in patients undergoing methadone maintenance treatment, with little consensus on their effect. This study aims to test the associatio...
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| creator | Chawar, Caroul Hillmer, Alannah Lamri, Amel Kapczinski, Flavio Thabane, Lehana Pare, Guillaume Samaan, Zainab |
| description | Genetic variants in the OPRM1 and CYP2B6 genes, respectively coding for an opioid receptor and methadone metabolizers, have been linked to negative treatment outcomes in patients undergoing methadone maintenance treatment, with little consensus on their effect. This study aims to test the associations between pre-selected SNPs of OPRM1 and CYP2B6 and outcomes of continued opioid use, relapse, and methadone dose. It also aims to observe differences in associations within the sexes. 1,172 participants treated with methadone (nMale = 666, nFemale = 506) were included in this study. SNPs rs73568641 and rs7451325 from OPRM1 and all the tested CYP2B6 SNPs were detected to be in high linkage disequilibrium. Though no associations were found to be significant, noteworthy differences were observed in associations of OPRM1 rs73568641 and CYP2B6 rs3745274 with treatment outcomes between males and females. Further research is needed to determine if sex-specific differences are present. |
| doi_str_mv | 10.1371/journal.pone.0261201 |
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This study aims to test the associations between pre-selected SNPs of OPRM1 and CYP2B6 and outcomes of continued opioid use, relapse, and methadone dose. It also aims to observe differences in associations within the sexes. 1,172 participants treated with methadone (nMale = 666, nFemale = 506) were included in this study. SNPs rs73568641 and rs7451325 from OPRM1 and all the tested CYP2B6 SNPs were detected to be in high linkage disequilibrium. Though no associations were found to be significant, noteworthy differences were observed in associations of OPRM1 rs73568641 and CYP2B6 rs3745274 with treatment outcomes between males and females. Further research is needed to determine if sex-specific differences are present.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0261201</identifier><identifier>PMID: 34910759</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Alleles ; Analgesics, Opioid - therapeutic use ; Biology and Life Sciences ; Clinical outcomes ; Complications and side effects ; Cytochrome P-450 CYP2B6 - genetics ; Cytochrome P-450 CYP2B6 - metabolism ; Drug dosages ; Female ; Gender aspects ; Gender differences ; Gene Frequency - genetics ; Genetic diversity ; Genetic variance ; Genomes ; Genotype ; Humans ; Linkage disequilibrium ; Linkage Disequilibrium - genetics ; Male ; Medical research ; Medicine and Health Sciences ; Mental disorders ; Metabolism ; Methadone ; Methadone - therapeutic use ; Methadone hydrochloride ; Narcotics ; Neurosciences ; Ontario - epidemiology ; Opiate Substitution Treatment - methods ; Opioid receptors ; Opioid-Related Disorders - drug therapy ; Patient outcomes ; Patients ; People and Places ; Polymorphism, Single Nucleotide - genetics ; Psychiatry ; Receptors, Opioid, mu - genetics ; Receptors, Opioid, mu - metabolism ; Recurrence ; Research methodology ; Sex Characteristics ; Sex differences ; Sex Factors ; Sexes ; Single-nucleotide polymorphism ; Substance-Related Disorders - genetics ; Substance-Related Disorders - metabolism ; Treatment Outcome</subject><ispartof>PloS one, 2021-12, Vol.16 (12), p.e0261201</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Chawar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Further research is needed to determine if sex-specific differences are present.</description><subject>Adult</subject><subject>Alleles</subject><subject>Analgesics, Opioid - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Clinical outcomes</subject><subject>Complications and side effects</subject><subject>Cytochrome P-450 CYP2B6 - genetics</subject><subject>Cytochrome P-450 CYP2B6 - metabolism</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Gender aspects</subject><subject>Gender differences</subject><subject>Gene Frequency - genetics</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Humans</subject><subject>Linkage disequilibrium</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mental disorders</subject><subject>Metabolism</subject><subject>Methadone</subject><subject>Methadone - therapeutic use</subject><subject>Methadone hydrochloride</subject><subject>Narcotics</subject><subject>Neurosciences</subject><subject>Ontario - epidemiology</subject><subject>Opiate Substitution Treatment - methods</subject><subject>Opioid receptors</subject><subject>Opioid-Related Disorders - drug therapy</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>People and Places</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychiatry</subject><subject>Receptors, Opioid, mu - genetics</subject><subject>Receptors, Opioid, mu - metabolism</subject><subject>Recurrence</subject><subject>Research methodology</subject><subject>Sex Characteristics</subject><subject>Sex differences</subject><subject>Sex Factors</subject><subject>Sexes</subject><subject>Single-nucleotide polymorphism</subject><subject>Substance-Related Disorders - genetics</subject><subject>Substance-Related Disorders - metabolism</subject><subject>Treatment Outcome</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk-2K1DAYhYso7rp6B6IBQfDHjPlo02R_COuw6sDKLOsH-CukaTKTpU3GJF3GG_C6zex0lxlQsKW0vHnOyctp3qJ4juAUkRq9vfZDcLKbrr3TU4gpwhA9KI4RJ3hCMSQP976PiicxXkNYEUbp4-KIlBzBuuLHxe95v-6sksl6F4E3YHF59RkB6Vow-3GJ31NwI4OVLuVFB1LQMvXaJeCHpHyvI7AO9DqtZJvbmPTSupQf3YJ1ttRbWQYWuRisPwXnm3Xng3VLEPUGtNYYHbRTOj4tHhnZRf1sfJ8U3z6cf519mlwsPs5nZxcTRTlOk1rWmDaQk7I12CjeMNNQVTW0ZIjrfDUlVo2uW1xBSWklMa84I8xwwiCvSnJSvNz55j6iGCOMIqcHCYeUokzMd0Tr5bVYB9vL8Et4acVtwYelkCFZ1WlhTFMRCiGnDJVly5qmgjVjpdJ1hbjZ7vZu3G1oet2qnEeQ3YHp4YqzK7H0N4LRmlBEs8Gr0SD4n4OO6R8tj9RS5q6sMz6bqd5GJc4oy8FhymCmpn-h8t3q3qr894zN9QPBmwNBZpLepKUcYhTzL1f_zy6-H7Kv99iVll1aRd8Nt0fwECx3oAo-xqDNfXIIiu0M3KUhtjMgxhnIshf7qd-L7g49-QNcXwIq</recordid><startdate>20211215</startdate><enddate>20211215</enddate><creator>Chawar, Caroul</creator><creator>Hillmer, Alannah</creator><creator>Lamri, Amel</creator><creator>Kapczinski, Flavio</creator><creator>Thabane, Lehana</creator><creator>Pare, Guillaume</creator><creator>Samaan, Zainab</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7182-0661</orcidid><orcidid>https://orcid.org/0000-0001-8935-5454</orcidid></search><sort><creationdate>20211215</creationdate><title>Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences</title><author>Chawar, Caroul ; Hillmer, Alannah ; Lamri, Amel ; Kapczinski, Flavio ; Thabane, Lehana ; Pare, Guillaume ; Samaan, Zainab</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-7a726b0934df2fc9b8fb6c5b64819eeeeb42cbe7d250a665a2959838f93809543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Analgesics, Opioid - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Clinical outcomes</topic><topic>Complications and side effects</topic><topic>Cytochrome P-450 CYP2B6 - genetics</topic><topic>Cytochrome P-450 CYP2B6 - metabolism</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Gender aspects</topic><topic>Gender differences</topic><topic>Gene Frequency - genetics</topic><topic>Genetic diversity</topic><topic>Genetic variance</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Humans</topic><topic>Linkage disequilibrium</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Mental disorders</topic><topic>Metabolism</topic><topic>Methadone</topic><topic>Methadone - therapeutic use</topic><topic>Methadone hydrochloride</topic><topic>Narcotics</topic><topic>Neurosciences</topic><topic>Ontario - epidemiology</topic><topic>Opiate Substitution Treatment - methods</topic><topic>Opioid receptors</topic><topic>Opioid-Related Disorders - 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This study aims to test the associations between pre-selected SNPs of OPRM1 and CYP2B6 and outcomes of continued opioid use, relapse, and methadone dose. It also aims to observe differences in associations within the sexes. 1,172 participants treated with methadone (nMale = 666, nFemale = 506) were included in this study. SNPs rs73568641 and rs7451325 from OPRM1 and all the tested CYP2B6 SNPs were detected to be in high linkage disequilibrium. Though no associations were found to be significant, noteworthy differences were observed in associations of OPRM1 rs73568641 and CYP2B6 rs3745274 with treatment outcomes between males and females. Further research is needed to determine if sex-specific differences are present.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34910759</pmid><doi>10.1371/journal.pone.0261201</doi><tpages>e0261201</tpages><orcidid>https://orcid.org/0000-0001-7182-0661</orcidid><orcidid>https://orcid.org/0000-0001-8935-5454</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-12, Vol.16 (12), p.e0261201 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2610390661 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Alleles Analgesics, Opioid - therapeutic use Biology and Life Sciences Clinical outcomes Complications and side effects Cytochrome P-450 CYP2B6 - genetics Cytochrome P-450 CYP2B6 - metabolism Drug dosages Female Gender aspects Gender differences Gene Frequency - genetics Genetic diversity Genetic variance Genomes Genotype Humans Linkage disequilibrium Linkage Disequilibrium - genetics Male Medical research Medicine and Health Sciences Mental disorders Metabolism Methadone Methadone - therapeutic use Methadone hydrochloride Narcotics Neurosciences Ontario - epidemiology Opiate Substitution Treatment - methods Opioid receptors Opioid-Related Disorders - drug therapy Patient outcomes Patients People and Places Polymorphism, Single Nucleotide - genetics Psychiatry Receptors, Opioid, mu - genetics Receptors, Opioid, mu - metabolism Recurrence Research methodology Sex Characteristics Sex differences Sex Factors Sexes Single-nucleotide polymorphism Substance-Related Disorders - genetics Substance-Related Disorders - metabolism Treatment Outcome |
| title | Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T23%3A48%3A13IST&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=Implications%20of%20OPRM1%20and%20CYP2B6%20variants%20on%20treatment%20outcomes%20in%20methadone-maintained%20patients%20in%20Ontario:%20Exploring%20sex%20differences&rft.jtitle=PloS%20one&rft.au=Chawar,%20Caroul&rft.date=2021-12-15&rft.volume=16&rft.issue=12&rft.spage=e0261201&rft.pages=e0261201-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0261201&rft_dat=%3Cgale_plos_%3EA686922680%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=2610390661&rft_id=info:pmid/34910759&rft_galeid=A686922680&rft_doaj_id=oai_doaj_org_article_ffb53600968144d8bb507884ce7519f4&rfr_iscdi=true |