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.
Oneda
B
B
Unit of Biochemistry and Clinical Psychopharmacology, Department of Psychiatry, CHUV, Center of Psychiatric Neurosciences, Hospital of Cery, University of Lausanne, Lausanne, Switzerland.
Crettol
S
S
Bochud
M
M
Besson
J
J
Croquette-Krokar
M
M
Hämmig
R
R
Monnat
M
M
Preisig
M
M
Eap
C B
CB
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