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Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.

The pharmacogenomics journal | 2014

Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.

Pubmed ID: 24126707 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: U10 DA013046
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA13038
  • Agency: NIDA NIH HHS, United States
    Id: UG1 DA015815
  • Agency: NIDA NIH HHS, United States
    Id: P20 DA025995
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA01714
  • Agency: NIDA NIH HHS, United States
    Id: P60 DA005186
  • Agency: NIMH NIH HHS, United States
    Id: T32 MH014654
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA013043
  • Agency: NIDA NIH HHS, United States
    Id: P60DA05186
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA015815
  • Agency: NIDA NIH HHS, United States
    Id: P20DA025995
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA13043
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA013036
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA013045
  • Agency: NIMH NIH HHS, United States
    Id: T32MH014654
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA013038
  • Agency: NIDA NIH HHS, United States
    Id: U10 DA13045

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This is a list of tools and resources that we have found mentioned in this publication.


Haploview (tool)

RRID:SCR_003076

A Java based software tool designed to simplify and expedite the process of haplotype analysis by providing a common interface to several tasks relating to such analyses. Haploview currently allows users to examine block structures, generate haplotypes in these blocks, run association tests, and save the data in a number of formats. All functionalities are highly customizable. (entry from Genetic Analysis Software) * LD & haplotype block analysis * haplotype population frequency estimation * single SNP and haplotype association tests * permutation testing for association significance * implementation of Paul de Bakker's Tagger tag SNP selection algorithm. * automatic download of phased genotype data from HapMap * visualization and plotting of PLINK whole genome association results including advanced filtering options Haploview is fully compatible with data dumps from the HapMap project and the Perlegen Genotype Browser. It can analyze thousands of SNPs (tens of thousands in command line mode) in thousands of individuals. Note: Haploview is currently on a development and support freeze. The team is currently looking at a variety of options in order to provide support for the software. Haploview is an open source project hosted by SourceForge. The source can be downloaded at the SourceForge project site.

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PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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International HapMap Project (tool)

RRID:SCR_002846

THIS RESOURCE IS NO LONGER IN SERVICE, documented August 22, 2016. A multi-country collaboration among scientists and funding agencies to develop a public resource where genetic similarities and differences in human beings are identified and catalogued. Using this information, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors. All of the information generated by the Project will be released into the public domain. Their goal is to compare the genetic sequences of different individuals to identify chromosomal regions where genetic variants are shared. Public and private organizations in six countries are participating in the International HapMap Project. Data generated by the Project can be downloaded with minimal constraints. HapMap project related data, software, and documentation include: bulk data on genotypes, frequencies, LD data, phasing data, allocated SNPs, recombination rates and hotspots, SNP assays, Perlegen amplicons, raw data, inferred genotypes, and mitochondrial and chrY haplogroups; Generic Genome Browser software; protocols and information on assay design, genotyping and other protocols used in the project; and documentation of samples/individuals and the XML format used in the project.

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