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

B Oneda, S Crettol, M Bochud, J Besson… - The …, 2011 - nature.com
B Oneda, S Crettol, M Bochud, J Besson, M Croquette-Krokar, R Hämmig, M Monnat…
The pharmacogenomics journal, 2011nature.com
Abstract 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 …
Abstract
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.
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