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Genetic Variation in OPRD1 and the Response to Treatment for Opioid Dependence with Buprenorphine in European American Females.

Pharmacogenomics Journal 2014;14:303-308. [doi: 10.1038/tpj.2013.30]

Toni-Kim Clarke, PhD (University of Pennsylvania), Richard C. Crist, PhD (University of Pennsylvania), Alfonso Ang, PhD (Integrated Substance Abuse Programs, UCLA, PR Node), Lisa M. Ambrose-Lanci, PhD (University of Pennsylvania), Falk W. Lohoff, MD (University of Pennsylvania), Andrew J. Saxon, MD (VA Puget Sound Health Care System, PN Node), Walter Ling, MD (Integrated Substance Abuse Programs, UCLA, PR Node), Maureen Hillhouse, PhD (Integrated Substance Abuse Programs, UCLA, PR Node), R. Douglas Bruce, MD, MA (Yale University School of Medicine, NEC Node), George E. Woody, MD (University of Pennsylvania School of Medicine), Wade H. Berrettini, MD, PhD (University of Pennsylvania).

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 determine 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 outcomes 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 buprenophine. For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype. No significant associations were detected in males.

Conclusions: 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. (Article (Peer-Reviewed), PDF, English, 2014)

Keywords: Buprenorphine/Naloxone | Gender differences | Genetics | Opioid dependence | Pharmacological therapy | Suboxone | Women | Pharmacogenomics Journal (journal)

Document No: 1014, PMID: 24126707, PMCID: PMC3988270.

Submitted by Jack Blaine, NIDA CCTN, 7/23/2013.

Ambrose-Lanci, Lisa search
Ang, Alfonso search
Berrettini, Wade search
Bruce, R. Douglas search mail
Clarke, Toni-Kim search
Crist, Richard C. search mail
Hillhouse, Maureen search mail
Ling, Walter search mail
Lohoff, Falk W. search
Saxon, Andrew J. search mail
Woody, George E. search mail
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