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

beta-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in m-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. The Pharmacogenomics Journal (2011) 11, 258-266; doi:10.1038/tpj.2010.37; published online 1 June 2010