Ikeda M, Ozaki N, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y, Kishi T, Sekine Y, Iyo M, Harano M, Komiyama T, Yamada M, Sora I, Ujike H, Inada T, Iwata N
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
Genes Brain Behav. 2007 Feb;6(1):107-12. doi: 10.1111/j.1601-183X.2006.00237.x.
Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.
近期研究表明，AKT/糖原合酶激酶3（GSK3）信号级联可能与精神分裂症及甲基苯丙胺（METH）使用障碍的病理生理学相关。与该信号级联相关的一个重要分子是β - 抑制蛋白2（ARRB2）。因此，我们在日本人群（547例精神分裂症患者、177例METH使用障碍患者和546例对照）中对ARRB2基因与精神分裂症及METH使用障碍进行了遗传病例对照关联分析。在METH使用障碍中发现了“标签单核苷酸多态性（SNP）”的可能关联（rs1045280：基因型P = 0.0118，等位基因P = 0.00351；rs2036657：等位基因P = 0.0431；rs4790694：基因型P = 0.0167，等位基因P = 0.0202），但未发现与精神分裂症有关联。我们还评估了ARRB2、AKT1和GSK3B之间的基因 - 基因相互作用，我们之前已分别报道过这些疾病中的相关情况。然而，在我们的样本中未观察到相互作用。这是首次对ARRB2进行的关联分析，我们的结果表明ARRB2可能在METH使用障碍的病理生理学中发挥作用。
