Can RGS4 polymorphisms be viewed as credible risk factors for schizophrenia? A critical review of the evidence.
Can RGS4 polymorphisms be viewed as credible risk factors for schizophrenia? A critical review of the evidence.
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DOI：
10.1093/schbul/sbj058
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发表时间：
2006-04
影响因子：
6.6
通讯作者：
M. Talkowski;K. Chowdari;D. Lewis;V. Nimgaonkar
中科院分区：
文献类型：
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作者：
M. Talkowski;K. Chowdari;D. Lewis;V. Nimgaonkar
最近，精神分裂症（SZ）的推定易感基因数量激增。这些基因是在假定的发病机制、连锁和遗传关联研究的基础上确定的。虽然出现了几个有希望的候选者，但确定一个结论性的遗传风险因素仍然难以捉摸。如果证据来自这三个领域，那将是最令人信服的。在这篇综述中，我们认为这些证据与g蛋白信号传导4 （RGS4）的调节因子有关，这是一个定位于染色体1q23的基因。在死后脑样本中观察到RGS4 mRNA水平的疾病特异性变化；据报道在染色体1q23上有连锁；一些关联研究已经得出结论，存在显著的关联。后者得到了最近进行的荟萃分析的支持。因此，在这些结构域中都有暗示性的证据表明RGS4在SZ易感性中起作用。然而，类似于其他有希望的易感性候选者，遗传关联的性质，精确的多态性(s)赋予风险，以及该基因序列变异的功能含义尚不清楚。我们回顾了已发表的数据，并将其置于建议标准的背景下，以建立候选基因作为具有非孟德尔遗传模式的疾病的可信易感性因素。
There has been a recent explosion in the list of putative susceptibility genes for schizophrenia (SZ). These genes have been identified on the basis of presumed pathogenesis, linkage, and genetic association studies. While several promising candidates have arisen, identification of a conclusive genetic risk factor has remained elusive. The proof would be most compelling if it stemmed from all three of these domains. In this review, we consider such evidence in relation to the regulator of G-protein signaling 4 (RGS4), a gene localized to chromosome 1q23. Disorder-specific changes in RGS4 mRNA levels have been observed in post-mortem brain samples; linkage has been reported at chromosome 1q23; and several association studies have concluded that significant associations exist. The latter are supported by a recently conducted meta-analysis. Thus, there is suggestive evidence in each of these domains implicating a role for RGS4 in SZ susceptibility. However, analogous to other promising susceptibility candidates, the nature of the genetic association, the precise polymorphism(s) conferring risk, and the functional implications of sequence variation at this gene are unclear. We review the published data and place them in the context of suggested criteria for establishing a candidate gene as a credible susceptibility factor for disorders with non-Mendelian patterns of inheritance.