Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
Eur Psychiatry. 2010 Oct;25(6):314-9. doi: 10.1016/j.eurpsy.2009.11.011. Epub 2010 Jul 7.
Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.
肌营养不良结合蛋白 1（DTNBP1），也称为 dysbindin，被认为在调节谷氨酸能系统中起关键作用。虽然多巴胺途径在精神分裂症的发病机制中是重要的，但谷氨酸能功能障碍似乎可能导致精神分裂症的发展。DTNBP1 在大脑中广泛表达，在精神分裂症患者的大脑中水平降低，并且 DTNBP1 多态性与脑表达降低有关。尽管进行了许多遗传研究，但没有 DTNBP1 多态性与精神分裂症的发病机制密切相关。使用基于单倍型块的基因标记方法，我们对 DTNBP1 中的 13 个 SNP 进行了基因分型，以研究与 DTNBP1 和精神分裂症的可能关联。发现四个多态性与精神分裂症显着相关。最强的关联是在 7 号内含子中的 A/C SNP（rs9370822）中发现的。与 rs9370822 的 C 等位基因纯合的个体患精神分裂症的可能性是对照组的两倍半以上。其他多态性显示出较弱的关联，不太可能具有生物学意义。这些结果表明 DTNBP1 是精神分裂症风险的一个很好的候选基因，rs9370822 要么具有功能重要性，要么与功能性 SNP 处于不平衡状态，尽管我们的观察结果应谨慎看待，直到它们被独立复制。
