Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Int J Neuropsychopharmacol. 2013 Feb;16(1):47-53. doi: 10.1017/S146114571200017X. Epub 2012 Mar 8.
The Asn40Asp variant (A118G) of the μ opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BP(ND)) of the μ-selective ligand [(11)C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BP(ND) at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.
阿片μ受体（OPRM1）基因的 Asn40Asp 变体（A118G）被认为有助于酒精依赖的发展和治疗。本研究采用正电子发射断层扫描（PET）技术，首先在健康对照（Con）和 5 天酒精戒断的酒精依赖（AD）受试者（未阻断基础扫描）中，检验该单核苷酸多态性（SNP）是否改变 μ 选择性配体[11C]carfentanil 的结合潜能（BP（ND））。其次，我们检验等位基因变异是否与 AD 受试者中纳曲酮（50mg）对 OPRM1 占有率的差异有关。在基础扫描中，携带 G 等位基因（AG）的 Con 和 AD 携带者的全局 BP（ND）低于纯合 A 等位基因（AA）的携带者。在 AD 受试者中，AG 受试者的纳曲酮占有率（98.9%）略高于 AA 受试者（93.1%），但无统计学意义。本研究首次在健康正常人和 AD 受试者中应用 PET 证明，A118G SNP 改变了 OPRM1 的可用性。
