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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 volume 14, pages 303–308 (2014)Cite this article

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Abstract

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.

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Acknowledgements

Main START study funding came from the National Institute on Drug Abuse through the Clinical Trials Network (CTN) through a series of grants provided to each participating node: the Pacific Northwest Node (U10 DA01714), the Oregon Hawaii Node (U10 DA013036), the California/Arizona Node (U10 DA015815), the New England Node (U10 DA13038), the Delaware Valley Node (U10 DA13043), the Pacific Region Node (U10 DA13045) and the New York Node (U10 DA013046). Dr Berrettini was also supported by the Delaware Valley Node (U10 DA13043). This work was supported by the Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Training Program in Neuropsychopharmacology (T32MH014654, PI: I Lucki), NIDA grant P20DA025995 (PI: W Berrettini), the Veterans Administration Mental Illness Research Education and Clinical Center MIRECC) at the Philadelphia VAMC (David Oslin, MD, PI) and NIDA grant P60DA05186 (PI: Charles O’Brien).

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  1. Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    T-K Clarke, R C Crist, L M Ambrose-Lanci, F W Lohoff & W H Berrettini

  2. Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA

    A Ang, W Ling & M P Hillhouse

  3. Veteran's Affairs Puget Sound Health Care System, Seattle, WA, USA

    A J Saxon

  4. Yale University School of Medicine, New Haven, CT, USA

    R D Bruce

  5. Perelman School of Medicine at the University of Pennsylvania and Treatment Research Institute, Philadelphia, PA, USA

    G Woody

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Competing interests

AJ Saxon is a paid consultant to Reckitt Benckiser Pharmaceuticals; W Ling is a paid consultant to Reckitt Benckiser Pharmaceuticals; RD Bruce research grant was supported by Gilead Sciences, Merck, Bristol Myers Squibb, Boehringer Ingelheim, Reckitt Benckiser Pharmaceuticals, Abbott Laboratories, Pfizer and honorarium from Reckitt Benckiser Pharmaceuticals. The remaining authors declare no conflict of interest.

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Clarke, TK., Crist, R., Ang, A. et al. Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females. Pharmacogenomics J 14, 303–308 (2014). https://doi.org/10.1038/tpj.2013.30

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