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FASEB J:血样表观遗传变化可能指示精神分裂症

来源:生物谷 2012-03-27 23:40

瑞典医科大学卡罗林斯卡医学院的研究人员完成的一项新研究中,研究人员已经确定了精神分裂症患者的血液中的表型遗传改变(又称DNA甲基化)。将来,这个新发现或许可用于开发出一种诊断精神分裂症患者的简单测试方法。

精神分裂症是我们最常见的慢性精神疾病之一,影响人口的1%。如果家庭成员有一个人患有这种疾病,那么其他人患精神分裂症患者的风险会增加。同时,研究表明具有相同基因组成的同卵双胞胎,遗传因素使得它们患这种疾病的风险高达50%。这表明环境因素是引发该疾病其余50%的原因,其中就包括基因组的表观遗传变化。

表观遗传学是研究基因的核苷酸序列不发生改变的情况下,基因表达了可遗传的变化的一门遗传学分支学科。表观遗传的现象很多,已知的有DNA甲基化(DNA methylation),基因组印记(genomic impriting),母体效应(maternal effects),基因沉默(gene silencing),核仁显性,休眠转座子激活和RNA编辑(RNA editing)等。我们的研究结果表明表观遗传机制在精神病中的重要意义。分子医学中心(CMM)Tomas Ekstrm教授说:这是特别有趣的是,这些表观遗传变化也与疾病发病年龄有关。

发表在FASEB杂志上的研究表明精神分裂症患者的白血细胞中DNA甲基化水平大大低于正常值,并且DNA甲基化的程度与发病年龄和疾病的严重程度有关。研究人员还分析比较了一直服用各类治疗药物的患者样本中甲基化的程度。结果发现,服用同一种类型的抗精神病药物接受治疗可能会影响DNA甲基化的水平,使得越来越趋向于正常水平。发表在FASEB杂志上的文章中,分子医学中心(CMM)的研究人员注意到目前还没有适合用于临床采样的精神分裂症的“生物标志物”。因此这可能是一个有趣的领域,应用新的研究发现开发出诊断精神分裂症的简单测试,并帮助监测患者接受治疗的反应情况。

研究人员Martin Schalling教授说:一份普通血液样本中的DNA甲基化可作为精神分裂症严重程度的标志为精神分裂症的诊断带来了新的机遇。但后续研究需要澄清例如治疗方法的选择是否与这一测试类型挂钩等问题。(生物谷:Bioon)

Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset

Philippe A. Melas, Maria Rogdaki, Urban sby, Martin Schalling, Catharina Lavebratt & Tomas J. Ekstrm

Even though schizophrenia has a strong hereditary component, departures from simple genetic transmission are prominent. DNA methylation has emerged as an epigenetic explanatory candidate of schizophrenia's nonmendelian characteristics. To investigate this assumption, we examined genome-wide (global) and gene-specific DNA methylation levels, which are associated with genomic stability and gene expression activity, respectively. Analyses were conducted using DNA from leukocytes of patients with schizophrenia and controls. Global methylation results revealed a highly significant hypomethylation in patients with schizophrenia (P<2.0×10??6) and linear regression among patients generated a model in which antipsychotic treatment and disease onset explained 11% of the global methylation variance (adjusted R2=0.11, ANOVA P<0.001). Specifically, haloperidol was associated with higher (“control-like”) methylation (P=0.001), and early onset (a putative marker of schizophrenia severity) was associated with lower methylation (P=0.002). With regard to the gene-specific methylation analyses, and in accordance with the dopamine hypothesis of psychosis, we found that the analyzed region of S-COMT was hypermethylated in patients with schizophrenia (P=0.004). In summary, these data support the notion of a dysregulated epigenome in schizophrenia, which, at least globally, is more pronounced in early-onset patients and can be partly rescued by antipsychotic medication. In addition, blood DNA-methylation signatures show promise of serving as a schizophrenia biomarker in the future.—Melas, P. A., Rogdaki, M., ??sby, U., Schalling, M., Lavebratt, C., Ekstr??m, T. J. Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset.

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