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β-Arrestin2 influences the response to methadone in opioid-dependent patients.
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.
Adolescent, Adult, Aged, Analgesics, Opioid/therapeutic use, Arrestins/genetics, Chi-Square Distribution, Cross-Sectional Studies, Female, Gene Frequency, Genotype, Humans, Individualized Medicine, Logistic Models, Male, Methadone/therapeutic use, Middle Aged, Odds Ratio, Opiate Substitution Treatment, Opioid-Related Disorders/genetics, Opioid-Related Disorders/rehabilitation, Pharmacogenetics, Phenotype, Polymorphism, Single Nucleotide, Retrospective Studies, Switzerland, Time Factors, Treatment Outcome, Young Adult
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