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.
Unit of Biochemistry and Clinical Psychopharmacology, Department of Psychiatry, CHUV, Center of Psychiatric Neurosciences, Hospital of Cery, University of Lausanne, Lausanne, Switzerland.
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B
Oneda
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Crettol
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Bochud
J
J
Besson
M
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Croquette-Krokar
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R
Hämmig
M
M
Monnat
M
M
Preisig
C B
CB
Eap
D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D019390:Arrestins / Q000235:genetics*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D016017:Odds Ratio; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000235:genetics* / Q000534:rehabilitation*; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D012189:Retrospective Studies; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D000701:Analgesics, Opioid; D019390:Arrestins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D008691:Methadone