A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder

Henry R Kranzler, Kevin G Lynch, Richard C Crist, Emily Hartwell, Anne Le Moigne, Celine M Laffont, Anne C Andorn, Henry R Kranzler, Kevin G Lynch, Richard C Crist, Emily Hartwell, Anne Le Moigne, Celine M Laffont, Anne C Andorn

Abstract

Background: Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine.

Methods: We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS).

Results: Among AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04).

Conclusion: We found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.

Trial registration: ClinicalTrials.gov NCT02357901.

Keywords: Buprenorphine; delta-opioid receptor; opioid use disorder; pharmacogenetic; rs678849.

© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.

Figures

Figure 1.
Figure 1.
Proportion of opioid-positive urine drug screens by treatment and genotype groups in African Americans.
Figure 2.
Figure 2.
Proportion of opioid-positive urine drug screens by treatment and genotype groups in European Americans.

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Source: PubMed

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