Alyssa C Feldner, Andrew K Turner, James F Simpson, Steven Estus
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引用次数: 0
Abstract
Background: Understanding the mechanisms whereby genetic variants influence the risk of Alzheimer's disease (AD) may provide insights into treatments that could reduce AD risk.
Objective: Here, we sought to test the hypothesis that a single nucleotide polymorphism (SNP) associated with AD risk, rs2070902, influences splicing of FCER1G exon 2.
Methods: AD and non-AD brain samples were analyzed for FCER1G expression by genotyping, immunohistochemistry, immunofluorescence, and qPCR.
Results: The protein encoded by FCER1G, FcRγ, is robustly expressed in microglia in both AD and non-AD brain. The FCER1G isoform lacking exon 2 (D2-FCER1G) was readily detectable. Moreover, the proportion of FCER1G expressed as this isoform was increased in brains with high AD neuropathology. However, the proportion of FCER1G expressed as the D2-FCER1G isoform was not associated with rs2070902 genotype.
Conclusions: In summary, the proportion of FCER1G expressed as the D2-FCER1G isoform is increased with AD neuropathology but is not associated with rs2070902.
背景：了解基因变异对阿尔茨海默病（AD）风险的影响机制可为降低阿尔茨海默病风险的治疗方法提供启示：目的：在此，我们试图检验与AD风险相关的单核苷酸多态性（SNP）rs2070902影响FCER1G外显子2剪接的假设：通过基因分型、免疫组织化学、免疫荧光和 qPCR 分析 AD 和非 AD 脑样本中 FCER1G 的表达：结果：FCER1G编码的蛋白FcRγ在AD和非AD大脑的小胶质细胞中均有强表达。缺失第2外显子的FCER1G异构体（D2-FCER1G）很容易被检测到。此外，在AD神经病理程度较高的大脑中，以这种异构体形式表达的FCER1G比例有所增加。然而，以D2-FCER1G异构体表达的FCER1G比例与rs2070902基因型无关：总之，FCER1G以D2-FCER1G同工酶形式表达的比例随AD神经病理学的发展而增加，但与rs2070902无关。
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