科学家(上海交大）鉴定出了精神分裂症易感基因

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http://www.journals.uchicago.edu/press/012307_AJHG.html

Embargoed Release: January 23, 2007
Contact: Suzanne Wu / 773-834-0386 /swu@press.uchicago.edu

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Scientists identify gene that may indicate predisposition to schizophrenia

In a new study from The American Journal of Human Genetics, a research team lead by Xinzhi Zhao and Ruqi Tang (Shanghai Jiao Tong University) present evidence that genetic variation may indicate predisposition to schizophrenia. Specifically, their findings identify the chitinase 3-like 1 gene as a potential schizophrenia-susceptibility gene and suggest that the genes involved in biological response to adverse conditions are likely linked to schizophrenia.

Analyzing two separate cohorts of Chinese patients with schizophrenia, the researchers observed a positive association between schizophrenia and genetic variations in the promoter region of the chitinase 3-like 1 (CHI3L1) gene, an association that was significant in both population-based and family-based investigations.

The CHI3L1 gene acts as a survival factor in response to adverse environments, countering various types of physiological stress, such as inflammation, nutrient deprivation, and oxygen deficiency, all of which may induce high expression of CHI3L1. The gene is located on chromosome 1q32.1, a region that has been previously shown to have a weak correlation to schizophrenia.

A number of environmental factors, including prenatal exposure to disease, have been reported as risk factors of schizophrenia. However, the researchers argue that sensitivity to environmental stressors varies widely among individuals, and “at least part of this variation may be genetic in origin and/or involve gene-environment factors,” they write.

Genetic variations that change the expression of CHI3L1 can influence key processes dependent on CHI3L1 levels, knocking out portions of the AKT-mediated signal pathway. The AKT-mediated signal pathway has been shown to be impaired in patients with schizophrenia, and antipsychotic medication may induce AKT activation, to compensate for the impairment. Additionally, activation of the inflammatory response has been observed in those with schizophrenia and other affective disorders.

“In conclusion, our findings identify CHI3L1 as a potential schizophrenia-susceptibility gene,” write the authors. “Our results . . . support the proposal that genes involved in biological response to adverse environmental conditions play roles in the predisposition to schizophrenia.”
据芝加哥大学出版社1月23日报道：《美国人类遗传学杂志》中的一项新研究中，由上海交通大学的Xinzhi Zhao和 Ruqi Tang 领导的研究小组提出证据证明，基因变异可能表明对精神分裂症的易感性。具体地说，他们的研究鉴定几丁质酶3样1（chitinase 3-like 1）基因是一个潜在的精神分裂症易感基因，并且提示负责机体对不利环境产生生物反应的基因很可能与精神分裂症相关。
研究者通过分析两组独立的中国精神分裂症患者队列，发现了精神分裂症与CHI3L1基因启动子区域的基因变异存在正相关，这种联系在以人群为基础的和以家族为基础的调查中都具有显著性。CHI3L1基因在机体对不利环境的反应中起着存活因子的角色，对抗着各种类型的生理应激，比如炎症，营养缺乏和氧气缺乏，这些都能引起CHI3L1的高表达。这个基因定位于染色体1q32.1，这个区域以前就被发现与精神分裂症存在弱的相关性。包括出生前暴露于疾病在内的大量的环境因素，被报道是精神分裂症的危险因素。然而，研究者争辩说，对于环境应激因素的敏感性在个体中存在很大的差异，“这些差异至少一部分可能是源于基因的和/或包括基因-环境因素。”他们写道。基因变异导致CHI3L1的表达变化可以影响依赖于CHI3L1水平的关键过程，导致部分敲除AKT介导的信号通路。AKT介导的信号通路在精神分裂症患者中发现有受损，而抗精神分裂症药物可以导致AKT激活，补偿这种受损。另外，炎症反应激活在精神分裂症和其他情感障碍中也被观察到。“总而言之，我们的发现鉴定出CHI3L1 是一个潜在的精神分裂症易感基因”作者写道，“我们的结果，支持了负责机体对不利环境条件产生生物反应的基因在精神分裂症的易感性中起作用的提议。”