Unit of Biochemistry and Clinical Psychopharmacology, Department of Psychiatry, CHUV, Center of Psychiatric Neurosciences, Hospital of Cery, University of Lausanne, Lausanne, Switzerland.
Pharmacogenomics J. 2011 Aug;11(4):258-66. doi: 10.1038/tpj.2010.37. Epub 2010 Jun 1.
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.
β-arrestin2（ARRB2）是 G 蛋白偶联受体复合物的一个组成部分，参与μ-阿片受体和多巴胺 D2 受体信号转导，这是美沙酮信号转导的两个核心过程。我们分析了 238 名接受美沙酮维持治疗（MMT）的患者，确定了一个横跨 ARRB2 基因座的单倍型块（rs34230287、rs3786047、rs1045280 和 rs2036657）。虽然这些单核苷酸多态性（SNP）没有导致氨基酸序列发生变化，但我们发现，在所分析的所有 SNP 中，除了 rs34230287 之外，变异等位基因的纯合子赋予了无反应表型（n=73；rs1045280C 和 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），这也反映在阴性尿液筛查的时间缩短了 12 倍（P=0.01）。因此，ARRB2 基因型可能有助于解释个体对 MMT 反应的变异性，并有助于预测治疗反应。
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