Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27958381
TITLE
A polymorphism in the OPRM1 3'-untranslated region is associated with methadone efficacy in treating opioid dependence.
ABSTRACT
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.
DATE PUBLISHED
2016 Dec 13
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Crist RC Crist R C RC Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, PA, Pennsylvania, USA.
Doyle GA Doyle G A GA 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 National Drug and Alcohol Research Centre, UNSW Australia, Sydney, New South Wales, Australia.
Martin NG Martin N G NG 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 Veteran's Affairs Puget Sound Health Care System, Seattle, WA, USA.
Ling W Ling W W University of California, Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA, USA.
Berrettini WH Berrettini W H WH Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, PA, Pennsylvania, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: The pharmacogenomics journal
ISOABBREVIATION: Pharmacogenomics J.
YEAR: 2016
MONTH: Dec
DAY: 13
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1473-1150
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Pharmacogenomics J
COUNTRY: United States
ISSNLINKING: 1470-269X
NLMUNIQUEID: 101083949
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
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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