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Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

The Pharmacogenomics Journal volume 19, pages 260–268 (2019)Cite this article

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Abstract

Many patients with opioid use disorder do not have successful outcomes during treatment but the underlying reasons are not well understood. An OPRD1 variant (rs678849) was previously associated with methadone and buprenorphine efficacy in African–Americans with opioid use disorder. The objective of this study was to determine if the effect of rs678849 on opioid use disorder treatment outcome could be replicated in an independent population. Participants were recruited from African–American patients who had participated in previous studies of methadone or buprenorphine treatment at the outpatient treatment research clinic of the NIDA Intramural Research Program in Baltimore, MD, USA between 2000 and 2017. Rs678849 was genotyped retrospectively, and genotypes were compared with urine drug screen results from the previous studies for opioids other than the one prescribed for treatment. Genotypes were available for 24 methadone patients and 55 buprenorphine patients. After controlling for demographics, the effect of rs678849 genotype was significant in the buprenorphine treatment group (RR = 1.69, 95% confidence interval (CI) 1.59–1.79, p = 0.021). Buprenorphine patients with the C/C genotype were more likely to have opioid-positive drug screens than individuals with the C/T or T/T genotypes, replicating the original pharmacogenetic finding. The effect of genotype was not significant in the methadone group (p = 0.087). Thus, the genotype at rs678849 is associated with buprenorphine efficacy in African–Americans being treated for opioid use disorder. This replication suggests that rs678849 genotype may be a valuable pharmacogenetic marker for deciding which opioid use disorder medication to prescribe in this population.

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Acknowledgements

START study funding came from the National Institute on Drug Abuse (NIDA) 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). Protocol 326, Protocol 385, Protocol 407, and Protocol 020 were supported by the Intramural Research Program of the NIH NIDA. Dr. Berrettini was supported by the Delaware Valley Node of the CTN (U10 DA13043) and by NIDA grant R21 DA036808. Dr. Crist was supported by NIDA grant K01 DA036751. Drs. Crist, Berrettini, and Doyle were supported by NIDA grant R01 DA044015. The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

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

    Richard C. Crist, Glenn A. Doyle & Wade H. Berrettini

  2. Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA

    Karran A. Phillips, Melody A. Furnari, Landhing M. Moran & Kenzie L. Preston

  3. Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, PA, USA

    Laura F. McNicholas, James W. Cornish & Kyle M. Kampman

  4. Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    James W. Cornish & Kyle M. Kampman

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Correspondence to Richard C. Crist.

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Conflict of interest

KMK has received consulting fees from Alkermes and Opiant Pharmaceuticals. He has also received grant funding from Alkermes, Opiant Pharmaceuticals, and Indivior. WHB has received consulting fees from Mundipharma and Geisinger Health Systems and grant support from Saniona. The remaining authors declare no conflict of interests.

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Crist, R.C., Phillips, K.A., Furnari, M.A. et al. Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder. Pharmacogenomics J 19, 260–268 (2019). https://doi.org/10.1038/s41397-018-0065-x

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