Case–control association analysis of polymorphisms in the delta-opioid receptor, OPRD1 , with cocaine and opioid addicted populations

• Published in: Drug and alcohol dependence Vol. 127; no. 1; pp. 122 - 128
• Main Authors: Crist, R.C, Ambrose-Lanci, L.M, Vaswani, M, Clarke, T.K, Zeng, A, Yuan, C, Ferraro, T.N, Hakonarson, H, Kampman, K.M, Dackis, C.A, Pettinati, H.M, O’Brien, C.P, Oslin, D.W, Doyle, G.A, Lohoff, F.W, Berrettini, W.H
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01-01-2013; Elsevier
• Subjects: Addiction; Addictive behaviors; Adult and adolescent clinical studies; Association study; Biological and medical sciences; Black American people; Black or African American - genetics; Case-Control Studies; Cocaine; Cocaine-Related Disorders - diagnosis; Cocaine-Related Disorders - genetics; Delta-opioid receptor; Drug addiction; Epidemiology; Female; General aspects; Genes; Genetics; Humans; Male; Medical sciences; Miscellaneous; Opioid-Related Disorders - diagnosis; Opioid-Related Disorders - genetics; Opioids; OPRD1; Polymorphism, Single Nucleotide - genetics; Population Surveillance - methods; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Public health. Hygiene; Public health. Hygiene-occupational medicine; Receptors, Opioid, delta - genetics; White People - genetics; OPRD1; Association study; Genetics; Addiction; Delta-opioid receptor; Human; Drug addiction; Illicit drug; Opiates; Case control study; δ Opioid receptor; Epidemiology; Ester; Association; Analysis; Population; Cocaine; Drug of abuse; Public health; Polymorphism
• ISSN: 0376-8716; 1879-0046; 1879-0046
• DOI: 10.1016/j.drugalcdep.2012.06.023

Abstract Background Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR). Methods The present study evaluated the contribution of OPRD1 , the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n = 336, CA n = 503) and European American (OA n = 1007, CA n = 336) populations. Results The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p = 0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p = 4.53 × 10−5 ; n = 993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p = 8.5 × 10−7 ) ( p -values non-FDR corrected). Conclusion The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.