Ambrose-Lanci Lisa M, Vaswani Meera, Clarke Toni-Kim, Zeng Angela, Lohoff Falk W, Ferraro Thomas N, Berrettini Wade H
Translational Research Laboratory, Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, 125 S. 31st St, School of Medicine, Rm. 2109, Philadelphia, PA 19104, USA.
Psychiatr Genet. 2012 Jun;22(3):141-5. doi: 10.1097/YPG.0b013e3283539528.
The rewarding properties of drugs of abuse are mediated by the mu-opioid receptor (MOR). Genetic variations in MOR and MOR interacting proteins (MORIPs) involved in MOR signaling may increase the risk for drug dependence. The MORIP β-arrestin plays an important role in the regulation of MOR trafficking, thereby highlighting it as a candidate gene for addiction phenotypes. In this case-control association study, DNA samples from cocaine-dependent (n=336) and opioid-dependent (n=335) patients and controls (n=656) were genotyped for seven single nucleotide polymorphisms (rs11868227, rs3786047, rs4522461, rs1045280, rs2271167, rs2036657, and rs4790694) across ARRB2, the gene encoding the β-arrestin 2 protein. No significant differences were observed in genotype or allele frequency between drug-dependent and control individuals for any of the single nucleotide polymorphisms analyzed. Haplotype analysis was similarly negative. Further studies are needed to determine whether variations in ARRB2 (or other MORIPs) are relevant to cocaine or opioid dependence in different ethnic populations or whether they confer a risk that is specific to dependence on other drugs of abuse.
滥用药物的奖赏特性由μ-阿片受体(MOR)介导。MOR及参与MOR信号传导的MOR相互作用蛋白(MORIPs)的基因变异可能会增加药物依赖风险。MORIPβ-抑制蛋白在MOR转运调节中起重要作用,因此将其作为成瘾表型的候选基因。在这项病例对照关联研究中,对来自可卡因依赖患者(n = 336)、阿片类药物依赖患者(n = 335)和对照者(n = 656)的DNA样本进行基因分型,检测编码β-抑制蛋白2的ARRB2基因上的7个单核苷酸多态性(rs11868227、rs3786047、rs4522461、rs1045280、rs2271167、rs2036657和rs4790694)。在所分析的任何单核苷酸多态性中,药物依赖个体与对照个体之间在基因型或等位基因频率上均未观察到显著差异。单倍型分析结果同样为阴性。需要进一步研究以确定ARRB2(或其他MORIPs)的变异是否与不同种族人群中的可卡因或阿片类药物依赖相关,或者它们是否会带来对其他滥用药物依赖特有的风险。