Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Schizophr Res. 2010 Jul;120(1-3):159-66. doi: 10.1016/j.schres.2010.03.041. Epub 2010 May 8.
Association with schizophrenia of the Abelson Helper Integration Site 1 (AHI1) gene on chromosome 6q23 and the adjacent primate-specific gene, C6orf217, was demonstrated in an inbred, Arab Israeli family sample and replicated in an Icelandic case control sample. Further support was provided by a second replication in a large European sample and a meta-analysis that supported association with schizophrenia of all seven alleles overtransmitted to affected subjects in the original study. We examined constitutive expression of AHI1 and C6orf217 in immortalized lymphoblasts of patients from the Arab Israeli family sample in which the association with schizophrenia was originally discovered and population-matched normal controls, and in post-mortem brain of patients with schizophrenia and bipolar (BP) disorder and control subjects from the Stanley Medical Research Institute Collection. We found a significant effect of diagnostic group in the lymphoblast sample (F=5.72; df=2,39; p=0.006). Patients with early age of onset had higher AHI1 expression than controls and later onset patients (p=0.002; 0.03 respectively). C6orf217 expression in lymphoblasts was too low to measure. We found no difference in brain expression of AHI1 in schizophrenia or BP patients compared to controls. However, there was a genotypic difference in AHI1 expression for SNP rs9321501, which was strongly associated with schizophrenia in the original study. Genotypes that included the undertransmitted C allele (CC/AC) showed lower expression than the homozygous AA genotype (F=4.73, df=2,83; p=0.028). There was no significant difference in brain expression of C6orf217 between patients and controls and no genotypic effect. This study provides further evidence for involvement of AHI1 in susceptibility to schizophrenia.
在一个近亲阿拉伯以色列家庭样本中，发现 Abelson Helper Integration Site 1 (AHI1) 基因与毗邻的灵长类特异性基因 C6orf217 与精神分裂症有关联，该基因位于染色体 6q23 上。这一发现随后在冰岛的病例对照样本中得到了复制。进一步的支持来自于对一个大型欧洲样本的第二次复制，以及一项荟萃分析，该分析支持了在原始研究中所有七个等位基因传递给受影响受试者与精神分裂症的关联。我们在最初发现与精神分裂症相关联的阿拉伯以色列家庭样本中的患者的永生淋巴母细胞和与之相匹配的正常对照中，以及在斯坦利医学研究所收藏的精神分裂症和双相（BP）障碍患者和对照中，检测了 AHI1 和 C6orf217 的组成型表达。我们发现，在淋巴母细胞样本中，诊断组有显著的影响（F=5.72；df=2,39；p=0.006）。与对照组相比，早发性患者的 AHI1 表达更高，而晚发性患者则更低（p=0.002；0.03）。淋巴母细胞中的 C6orf217 表达过低而无法测量。我们发现，与对照组相比，精神分裂症或 BP 患者的大脑中 AHI1 的表达没有差异。然而，在原始研究中与精神分裂症强烈相关的 SNP rs9321501 的 AHI1 表达存在基因型差异。包含低传递 C 等位基因（CC/AC）的基因型表达低于纯合 AA 基因型（F=4.73，df=2,83；p=0.028）。患者和对照组之间的大脑 C6orf217 表达没有显著差异，也没有基因型影响。这项研究提供了进一步的证据，证明 AHI1 参与了精神分裂症的易感性。
