PNAS：DNA删除可能防止双相情感障碍

继续研究

一项新的研究表明，在一个特定基因中缺乏一小段DNA可以防止人体出现双相情感障碍。谷氨酸是一种神经递质，即在神经元之间传递信号的分子。大脑的谷氨酸信号传导的破坏与几种精神病有联系。
Ben Pickard及其同事此前发现了一个谷氨酸受体基因（GRIK4）的一个区域和双相情感障碍的发病风险降低有关。这组科学家如今把注意力集中在了产生这种保护效果的DNA变异上：这是跟随着该基因的一个非编码区的一个删除。他们的统计分析表明在这个DNA删除和不存在双相情感障碍之间有强有力的联系，而且他们在针对第二群人的研究中成功地重复了这一分析。这个基因删除看上去增加了负责制造更多的谷氨酸受体的信使RNA的水平。
这组科学家说，这些结果提示它有可能让医生用增加受体活性的药物治疗双相情感障碍，补偿患者体内表达的减少。(生物谷Biooncom)
生物谷推荐原始出处:
PNAS published September 29, 2008, doi:10.1073/pnas.0800643105

A common variant in the 3′UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder

B. S. Pickard, H. M. Knight, R. S. Hamilton, D. C. Soares, R. Walker, J. K. F. Boyd, J. Machell, A. Maclean, K. A. McGhee, A. Condie, D. J. Porteous, D. Clair, I. Davis, D. H. R. Blackwood, and W. J. Muir

Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3′ end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3′ untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression.

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