Dataset Information

Association study of the ?-arrestin 2 gene (ARRB2) with opioid and cocaine dependence in a European-American population.

ABSTRACT: The rewarding properties of drugs of abuse are mediated by the mu-opioid receptor (MOR). Genetic variations in MOR and MOR interacting proteins (MORIPs) involved in MOR signaling may increase the risk for drug dependence. The MORIP ?-arrestin plays an important role in the regulation of MOR trafficking, thereby highlighting it as a candidate gene for addiction phenotypes. In this case-control association study, DNA samples from cocaine-dependent (n=336) and opioid-dependent (n=335) patients and controls (n=656) were genotyped for seven single nucleotide polymorphisms (rs11868227, rs3786047, rs4522461, rs1045280, rs2271167, rs2036657, and rs4790694) across ARRB2, the gene encoding the ?-arrestin 2 protein. No significant differences were observed in genotype or allele frequency between drug-dependent and control individuals for any of the single nucleotide polymorphisms analyzed. Haplotype analysis was similarly negative. Further studies are needed to determine whether variations in ARRB2 (or other MORIPs) are relevant to cocaine or opioid dependence in different ethnic populations or whether they confer a risk that is specific to dependence on other drugs of abuse.

SUBMITTER: Ambrose-Lanci LM

PROVIDER: S-EPMC3920286 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Association study of the β-arrestin 2 gene (ARRB2) with opioid and cocaine dependence in a European-American population.

Ambrose-Lanci Lisa M LM Vaswani Meera M Clarke Toni-Kim TK Zeng Angela A Lohoff Falk W FW Ferraro Thomas N TN Berrettini Wade H WH

Psychiatric genetics 20120601 3

The rewarding properties of drugs of abuse are mediated by the mu-opioid receptor (MOR). Genetic variations in MOR and MOR interacting proteins (MORIPs) involved in MOR signaling may increase the risk for drug dependence. The MORIP β-arrestin plays an important role in the regulation of MOR trafficking, thereby highlighting it as a candidate gene for addiction phenotypes. In this case-control association study, DNA samples from cocaine-dependent (n=336) and opioid-dependent (n=335) patients and ...[more]

PMID: 22472784

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Project description:AimSubstance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted.MethodsCox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of multiple substance dependence phenotypes were used to test for association between genetic variants and these outcomes. The top findings were tested for replication in two independent cohorts.ResultsIn the discovery sample, three independent regions containing variants associated with time to dependence at P < 5 x 10-8 were identified, one (rs61835088 = 1.03 x 10-8) for cocaine in the combined EA-AA meta-analysis in the gene FAM78B on chromosome 1, and two for opioids in the AA portion of the sample in intergenic regions of chromosomes 4 (rs4860439, P = 1.37 x 10-8) and 9 (rs7032521, P = 3.30 x 10-8). After meta-analysis with data from the replication cohorts, the signal at rs61835088 improved (HR = 0.87, P = 3.71 x 10-9 and an intergenic SNP on chromosome 21 (rs2825295, HR = 1.14, P = 2.57 x 10-8) that missed the significance threshold in the AA discovery sample became genome-wide significant (GWS) for CD.ConclusionsAlthough the two GWS variants are not in genes with obvious links to SUD biology and have modest effect sizes, they are statistically robust and show evidence for association in independent samples. These results may point to novel pathways contributing to disease progression and highlight the utility of related phenotypes to better understand the genetics of SUDs.

Dataset Information

Association study of the ?-arrestin 2 gene (ARRB2) with opioid and cocaine dependence in a European-American population.

Publications

Association study of the β-arrestin 2 gene (ARRB2) with opioid and cocaine dependence in a European-American population.

Similar Datasets

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