精神分裂症是大脑发育异常导致的严重精神疾病,科学家们正在对此开展基因学研究,以期找到精神分裂症的致病基因。2008年3月的爱思唯尔期刊《生物精神病学》(Biological Psychiatry)在显著位置刊登了一篇关于精神分裂症致病基因新发现的研究论文。
一项基因图谱研究发现,一个名为“MEGF10”的基因可能与精神分裂症的病理过程有关。此前的研究发现,MEGF10基因会影响人体表皮生长。在最新研究中,弗吉尼亚联邦大学医学院助理教授Xiangning Chen和同事直接对比分析了精神分裂症患者与普通人MEGF10基因的不同。他们发现,在家族基因研究和病例-对照基因研究中,MEGF10基因决定了精神分裂症的遗传风险。此外,研究人员通过尸体脑组织的解剖对比发现,MEGF10基因对脑部发育影响很大。
Chen说:“该文章的重要性在于,它表明了直接控制细胞凋亡的MEGF10基因与精神分裂症之间存在某种联系。科学家们一致怀疑是脑细胞凋亡紊乱引起了精神分裂症,却一直缺乏直接证据。细胞凋亡是人类和其它复杂生物体细胞程序性死亡的重要生物学过程,该过程的异常会导致很多疾病。”
《生物精神病学》杂志的编辑、耶鲁大学医学院的John H. Krystal博士评论说:“文章怀疑精神分裂症与MEGF10基因有关,而此前的研究发现MEGF10基因影响人体表皮生长。可以从两个方面来理解。一是在人类胚胎发育早期,神经细胞与皮肤细胞都起源于同一种类型的原胞。二是精神分裂症患者的表皮发育,例如指纹,与普通人相比会表现出异常。”
该论文表明,有必要进一步深入研究MEGF10基因,探索该基因如何影响大脑发育和如何改进精神分裂症治疗方法。(科学网 荔涛/编译)
生物谷推荐原始出处:
(Biological Psychiatry),doi:10.1016/j.biopsych.2007.11.003 ,Xiangning Chen, Kenneth S. Kendler
MEGF10 Association with Schizophrenia
Xiangning Chena, , , Xu Wanga, Qi Chena, Vernell Williamsona, Edwin van den Oordb, Brion S. Mahera, F. Anthony O’Neillc, Dermot Walshd and Kenneth S. Kendlera
aDepartment of Psychiatry, the Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA
bDepartment of Pharmacy and Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA
cDepartment of Psychiatry, The Queens University, Belfast, Northern Ireland
dThe Health Research Board, Dublin, Ireland.
Received 23 August 2007; revised 7 November 2007; accepted 8 November 2007. Available online 7 January 2008.
Background
The 5q21–31 region has been implicated as harboring risk genes for schizophrenia in many linkage studies. In our previous report of stepwise fine mapping of this region, the MEGF10 gene was one of the genes showing consistent associations in our screening subsample. In this study, we carried out independent replication and expression studies of the MEGF10 gene.
Methods
Association studies with 8 SNPs in the MEGF10 gene were performed in the Irish case-control study of schizophrenia (ICCSS) sample (652 case and 617 control subjects). The expression of MEGF10 was also compared between healthy control subjects and schizophrenia patients using postmortem brain cDNA libraries.
Results
In the ICCSS sample, associations with the disease were found in the same risk alleles and haplotypes as that observed in our fine-mapping studies. The major allele (A) of rs27388 was overrepresented in affected individuals (p = .0169), which remained significant after correction for multiple testing. In expression studies, MEGF10 had higher expression levels in the affected than the unaffected (p = .015). Schizophrenia patients with a 1/1 genotype at rs27388 had higher expressions than those patients with 1/2 and 2/2 genotypes (p = .0008).
Conclusions
Evidence from both association and expression studies suggests that MEGF10 is likely associated with schizophrenia. The major allele and 1/1 genotype at rs27388 impose higher risks for the disease.