摘要/Abstract

摘要： 目的 ·探讨早期生长反应基因 1（early growth response gene 1，EGR1）与中国汉族人群阿尔茨海默病（ Alzheimers disease， AD）发病风险的关联。方法 ·纳入 2个独立样本共计 715例 AD患者和 760例健康对照 (包括来自华东地区的 382例 AD患者和 426例健康对照以及来自西南地区的 333例 AD患者和 334例健康对照 )。采取外周静脉血并提取 DNA，利用 SNaPshot技术对单核苷酸多态性位点 rs11743810进行分型。结合公共数据库探索 EGR1基因在 AD患者和健康对照的大脑中是否存在差异表达；并通过 STRING数据库构建蛋白质 –蛋白质交互作用（ protein-protein interaction，PPI）网络图，以明确 EGR1与 AD高风险基因之间是否存在联系；采用表达数量性状基因座 ( quantitative trait loci，eQTL)关联分析探讨 rs11743810多态性与 AD易感性的关系。结果 ·差异表达分析发现，AD患者与健康对照脑内 EGR1基因在颞叶皮层表达存在显著差异（校正前 |log2FC|0.780，P0.000；FDR校正后 P0.001）。PPI结果也表明 EGR1蛋白与 AD高风险基因表达的蛋白如淀粉样蛋白前体（amyloid precursor protein，APP）以及载脂蛋白 J（clusterin，CLU）之间存在交互作用。然而， eQTL分析结果显示， EGR1基因单核苷酸多态性 rs11743810不同基因型在 10个脑区的表达无明显差异（校正后 P>0.05）。外周血 DNA样本分析结果也提示 AD组和健康对照组的 rs11743810位点基因型和等位基因分布频率的差异均无统计学意义（P>0.05）。结论 · rs11743810多态性位点可能不是中国汉族人群 AD的主要致病位点。
关键词: 阿尔茨海默病, 基因多态性, 早期生长反应基因 1, 表达数量性状基因座, 差异表达
Abstract:
Objective · To investigate the association between early growth response gene 1 (EGR1) and Alzheimers disease (AD) in Han Chinese people. Methods · A total of 715 AD patients and 760 health controls were recruited in two independent samples Eastern China (382 AD patients and 426 normal individuals) and Southwest China (333 AD patients and 334 normal individuals) . SNaPshot technique was utilized to analyse the single nucleotide polymorphism (SNP) of rs11743810. A public database was used to explore whether EGR1 gene was differentially expressed in the brain of AD patients and health controls. Then the protein-protein interaction (PPI) assessment was conducted using the STRING database, and the brain eQTL ( quantitative trait loci) analysis was used to explore the difference in rs11743810 between different genotypes in different brain regions. Results · Cross-platform normalized data showed that there was significant difference of EGR1 in temporal cortex between AD patients and control subjects (|log2FC|0.780, P0.000 before FDR corrected; P0.001 after FDR corrected). PPI analysis revealed that EGR1 was physically connected with amyloid precursor protein (APP) and clusterin (CLU) protein in the network. However, different genotypes of rs11743810 showed no significant difference in in 10 brain regions, and no significant difference in the genotype and allele frequency of rs11743810 between AD patients and controls were found in our two independent samples. Conclusion · The rs11743810 in EGR1 may not be major susceptibility gene site for AD in Han Chinese people.
Key words: Alzheimers disease, gene polymorphism, early growth response gene 1 (EGR1), quantitative trait loci (eQTL), differential


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