Maj Carlo, Minelli Alessandra, Giacopuzzi Edoardo, Sacchetti Emilio, Gennarelli Massimo
Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Viale Europa, 11 - 25123 Brescia, Italy.
Curr Neuropharmacol. 2016;14(5):540-50. doi: 10.2174/1570159x13666150514232745.
Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder.
基因组研究揭示了精神分裂症遗传结构中的两个主要组成部分,一个由决定分布式多基因效应的常见变异构成,另一个由大量异质性罕见且具有高度破坏性的突变代表。这些基因修饰常常影响神经传递,并且不同研究证明了代谢型谷氨酸受体与精神分裂症表型有关。通过将文献信息与来自公共数据库的基因组数据相结合,我们分析了目前关于人类代谢型谷氨酸受体基因变异与精神分裂症及相关内表型的关系的知识。尽管分析未揭示出明确的联系,但已确定了不同的提示性关联,特别是GRM3在影响特定精神分裂症内表型方面出现了相关作用。这支持了这些受体直接参与精神分裂症疾病的假说。