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

Oneda, B; Crettol, S; Bochud, M; Besson, J; Croquette-Krokar, M; Hämmig, R; Monnat, M; Preisig, M; Eap, C B (2011). β-Arrestin2 influences the response to methadone in opioid-dependent patients. Pharmacogenomics journal, 11(4), pp. 258-66. Basingstoke: Nature Publishing Group 10.1038/tpj.2010.37

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β-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in μ-opioid and dopamine D(2) 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > UPD Murtenstrasse

UniBE Contributor:

Hämmig, Robert

ISSN:

1470-269X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:39

Last Modified:

06 Dec 2013 13:37

Publisher DOI:

10.1038/tpj.2010.37

PubMed ID:

20514076

Web of Science ID:

000293122100003

URI:

https://boris.unibe.ch/id/eprint/15818 (FactScience: 223277)

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