Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Apr 16;34(3):506-9. doi: 10.1016/j.pnpbp.2010.02.005. Epub 2010 Feb 6.
Early growth response (EGR) genes are thought to have a role in the pathogenesis of schizophrenia because of their conserved DNA binding domain and biologically activity in neuronal plasticity. This zinc-finger motif could influence gene post-translational modification and expression. The multigenetic association model, using markers in genes of similar or antagonistic biological effects within a signal pathway or gene family, might be more appropriate to this aspect of the schizophrenia hypothesis than the single gene strategy. In this study we investigated the role of EGR1, EGR2, EGR3 and EGR4 within the EGR family. Taqman technology was used to examine 12 single nucleotide polymorphisms (SNPs) covering these four genes in 2044 Chinese Han subjects. Case-control analyses were performed to detect association of these 4 genes with schizophrenia and multifactor dimensionality reduction (MDR) analysis was employed to examine their potential gene-gene interaction in schizophrenia. Neither allelic nor genotypic single-locus tests revealed any significant association between EGR1-4 and the risk of schizophrenia nor was any such association found with regard to interaction within EGR1-4 (p(min)=0.623, CV Consistency=10/10). We concluded that although multiple candidate genes are involved in schizophrenogenic development, the EGR family may not play a major role in schizophrenia susceptibility in the Chinese Han population.
早期生长反应 (EGR) 基因被认为在精神分裂症的发病机制中起作用,因为它们具有保守的 DNA 结合域和在神经元可塑性中的生物学活性。这个锌指基序可能会影响基因的翻译后修饰和表达。多基因关联模型,使用信号通路或基因家族内具有相似或拮抗生物学效应的基因中的标记,可能比单个基因策略更适合精神分裂症假说的这一方面。在这项研究中,我们研究了 EGR 家族中 EGR1、EGR2、EGR3 和 EGR4 的作用。Taqman 技术用于检查这四个基因中的 12 个单核苷酸多态性 (SNP) 在 2044 名中国汉族受试者中。病例对照分析用于检测这些 4 个基因与精神分裂症的关联,多因子降维 (MDR) 分析用于检查它们在精神分裂症中的潜在基因-基因相互作用。等位基因或基因型单基因测试均未发现 EGR1-4 与精神分裂症风险之间存在任何显着关联,也未发现 EGR1-4 内的相互作用存在任何关联(p(min)=0.623,CV 一致性=10/10)。我们得出的结论是,尽管多个候选基因参与了精神分裂症的发生发展,但 EGR 家族可能在汉族人群中对精神分裂症易感性没有起主要作用。