Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders.
Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders.
复制标题
DOI：
10.1155/2013/965046
复制
发表时间：
2013
影响因子：
2.6
通讯作者：
Carter CJ
中科院分区：
文献类型：
--
作者：
Carter CJ
弓形虫不仅与精神分裂症和相关疾病有关，还与阿尔茨海默氏症或帕金森氏症、癌症、心脏肌病和自身免疫性疾病有关。在其生活史中，病原菌与约3000个寄主基因或蛋白相互作用。多发性硬化症、阿尔茨海默病、精神分裂症、躁郁症、抑郁症、儿童肥胖症、帕金森病、注意力缺陷多动障碍(P 从 8.01E−05 (ADHD) 到 1.22E−71)(多发性硬化症)和自闭症(P=0.013)的易感基因在这个互动组的人类手臂中高度丰富，18%(ADHD)至33%(MS)的易感基因与其相关。易感基因/相互作用组重叠中涉及的信号通路是相对特定的，与每种疾病相关，这表明了一种手段，即易感基因可以将单一病原体的注意力集中到破坏共同对不同疾病的内表型有贡献(积极或消极)的特定途径上。条件性蛋白敲除，由弓形虫蛋白或抗体与宿主结合(病原体产生的自身免疫)和代谢物交换协调，可能有助于这种破坏。因此，易感基因可能与疾病的起因和影响因素有关，而不是(以及)与疾病本身有关。
Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P from 8.01E − 05 (ADHD) to 1.22E − 71) (multiple sclerosis), and autism (P = 0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself.