Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Neurosci Res. 2013 Dec;77(4):222-7. doi: 10.1016/j.neures.2013.08.010. Epub 2013 Sep 4.
The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of neural development. Previous evidence from genetic association and biological studies implicates the DISC1 gene as having a role in the pathophysiology of schizophrenia. In the present study, we explored the association between DISC1 missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related haplotype block and schizophrenia in the Japanese population. We could not find a significant association of selected SNPs with schizophrenia after correction for multiple testing. We performed a meta-analysis of the Ser704Cys variant in schizophrenia using data from the present study and five previous Japanese population studies, and found no association with schizophrenia. We also examined DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia patients compared to control samples. The immunoreactivity revealed a significant decrease of DISC1 protein expression in the schizophrenia samples after ruling out potential confounding factors. However, the Ser704Cys variant did not show effects on DISC1 immunoreactivity. These results provide evidence that this functional genetic variation of DISC1 do not underlie the pathophysiology of schizophrenia in the Japanese population.
精神分裂症相关蛋白 1（DISC1）基因在神经发育的调控中发挥作用。先前的遗传关联和生物学研究证据表明，DISC1 基因在精神分裂症的病理生理学中发挥作用。在本研究中，我们探讨了 DISC1 错义突变 rs821616（Ser704Cys）单核苷酸多态性（SNP）与相关单倍型块中的其他四个 SNP（rs1772702、rs1754603、rs821621、rs821624）与日本人群中精神分裂症之间的关联。在进行多次检验校正后，我们没有发现所选 SNP 与精神分裂症之间存在显著关联。我们使用本研究和之前五项日本人群研究的数据对精神分裂症中 Ser704Cys 变体进行了荟萃分析，并未发现与精神分裂症相关。我们还比较了精神分裂症患者和对照样本死后前额叶皮质标本中的 DISC1 免疫反应性。排除潜在的混杂因素后，免疫反应显示精神分裂症样本中 DISC1 蛋白表达显著下降。然而，Ser704Cys 变体并未显示对 DISC1 免疫反应性的影响。这些结果表明，DISC1 的这种功能性遗传变异不是日本人群精神分裂症病理生理学的基础。
