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| PMID |
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| TITLE |
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| A polymorphism in the OPRM1 3'-untranslated region is associated with methadone efficacy in treating opioid dependence. |
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| ABSTRACT |
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NlmCategory: UNASSIGNED |
| The μ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for opioid dependence based on rs10485058 genotype might improve outcomes in this ethnic group.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.89. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2016/08/25 |
| revised |
2016/11/07 |
| accepted |
2016/11/14 |
| entrez |
2016/12/14 06:00 |
| pubmed |
2016/12/14 06:00 |
| medline |
2016/12/14 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Crist RC |
|
Crist |
R C |
RC |
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Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, PA, Pennsylvania, USA. |
| Doyle GA |
|
Doyle |
G A |
GA |
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Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, PA, Pennsylvania, USA. |
| Nelson EC |
|
Nelson |
E C |
EC |
|
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Degenhardt L |
|
Degenhardt |
L |
L |
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National Drug and Alcohol Research Centre, UNSW Australia, Sydney, New South Wales, Australia. |
| Martin NG |
|
Martin |
N G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Montgomery GW |
|
Montgomery |
G W |
GW |
|
The University of Queensland, Herston, Queensland, Australia. |
| Saxon AJ |
|
Saxon |
A J |
AJ |
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Veteran's Affairs Puget Sound Health Care System, Seattle, WA, USA. |
| Ling W |
|
Ling |
W |
W |
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University of California, Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA, USA. |
| Berrettini WH |
|
Berrettini |
W H |
WH |
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Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, PA, Pennsylvania, USA. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: The pharmacogenomics journal |
| ISOABBREVIATION: Pharmacogenomics J. |
| YEAR: 2016 |
| MONTH: Dec |
| DAY: 13 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1473-1150 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Pharmacogenomics J |
| COUNTRY: United States |
| ISSNLINKING: 1470-269X |
| NLMUNIQUEID: 101083949 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| K01 DA036751 |
NIDA NIH HHS |
United States |
| R01 DA017305 |
NIDA NIH HHS |
United States |
| R21 DA036808 |
NIDA NIH HHS |
United States |
| U10 DA013043 |
NIDA NIH HHS |
United States |
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