Ikeda Masashi, Iwata Nakao, Suzuki Tatsuyo, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Inada Toshiya, Ozaki Norio
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Biol Psychiatry. 2004 Nov 1;56(9):698-700. doi: 10.1016/j.biopsych.2004.07.023.
Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test.
We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP.
We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association.
Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.
V-akt小鼠胸腺瘤病毒癌基因同源物1（AKT1）异常可能是精神分裂症的一个易感因素。近期支持该假说的证据表明，精神分裂症患者的AKT1蛋白水平降低，且根据传递不平衡检验，AKT1单倍型存在显著关联。
我们使用相对较大的病例对照样本（507名日本精神分裂症患者和437名对照受试者）首次对该证据进行了重复验证。我们对原始研究中的5个单核苷酸多态性（SNP）以及另外1个SNP进行了基因分型。
我们发现与一个不同于原始研究结果（SNP3）的SNP（SNP5）存在正相关，并且由SNP5组合构建的单倍型也具有显著性。SNP5周围的连锁不平衡情况复杂，可能导致了这种正相关。
我们的研究为AKT1是日本精神分裂症的易感基因这一理论提供了支持。需要进行精细的连锁不平衡图谱分析才能得出确凿结果。
