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β-Arrestin2 influences the response to methadone in opioid-dependent patients

Abstract

β-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in μ-opioid and dopamine D2 receptor signaling, two central processes in methadone signal transduction. We analyzed 238 patients in methadone maintenance treatment (MMT) and identified a haplotype block (rs34230287, rs3786047, rs1045280 and rs2036657) spanning almost the entire ARRB2 locus. Although none of these single nucleotide polymorphisms (SNPs) leads to a change in amino-acid sequence, we found that for all the SNPs analyzed, with exception of rs34230287, homozygosity for the variant allele confers a nonresponding phenotype (n=73; rs1045280C and rs2036657G: OR=3.1, 95% CI=1.5–6.3, P=0.004; rs3786047A: OR=2.5, 95% CI=1.2–5.1, P=0.02) also illustrated by a 12-fold shorter period of negative urine screening (P=0.01). The ARRB2 genotype may thus contribute to the interindividual variability in the response to MMT and help to predict response to treatment.

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Acknowledgements

We thank V Sari, K Powell Golay (editorial assistance), E Ponce (bibliographical help), N Cochard, M Delessert, M Jonzier-Perey, M Brawand, AC Aubert, C Brogli (sample analysis). This work was supported by grants from the Swiss National Foundation (3200-065427.01 to CB Eap; 32-40677.94 and 3200B0-105969 to F Ferrero; 32-47315.96 and 32-061974.00 to M Preisig), a grant from the Swiss Federal Office of Public Health (02.001382 to CB Eap) as well as a research grant from GlaxoSmithKline (UNDHD2002/00002/00 to M Preisig). Role of the Funding Source: The funding sources have no role on the design, conduct and reporting of the study or in the decision to submit the article for publication.

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Oneda, B., Crettol, S., Bochud, M. et al. β-Arrestin2 influences the response to methadone in opioid-dependent patients. Pharmacogenomics J 11, 258–266 (2011). https://doi.org/10.1038/tpj.2010.37

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