Infante Jon, Llorca Javier, Mateo Ignacio, Rodríguez-Rodríguez Eloy, Sánchez-Quintana Coro, Sánchez-Juan Pascual, Fernández-Viadero Carlos, Peña Nicolás, Berciano José, Combarros Onofre
Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria, Santander, Spain.
Dement Geriatr Cogn Disord. 2007;23(4):215-8. doi: 10.1159/000099471. Epub 2007 Feb 9.
Excessive release of proinflammatory cytokines by activated microglia surrounding senile plaques might contribute to the neurodegeneration associated with Alzheimer's disease (AD). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear protein recently implicated in the initial inflammatory response by modulating expression of inflammation-related genes, like interleukin 1 (IL-1). As PARP-1 overactivity has been shown in the AD brain, we tested the hypothesis that the PARP-1 -410 and -1672 polymorphisms would predispose people to AD due to overexpression of the PARP-1 gene, independently or in concert with the proinflammatory IL-1A -889 polymorphism. So, we performed a case-control study in 263 Spanish AD patients and 293 healthy controls. PARP-1 -410 and PARP-1 -1672 haplotypes were associated with an increased risk for AD (global haplotype association p value=0.019), and, in addition, PARP-1 haplotypes increased the risk of AD by interaction with the IL-1A -889 allele 2.
围绕老年斑的活化小胶质细胞过度释放促炎细胞因子可能导致与阿尔茨海默病（AD）相关的神经退行性变。聚（ADP-核糖）聚合酶1（PARP-1）是一种核蛋白，最近发现其通过调节炎症相关基因（如白细胞介素1（IL-1））的表达参与初始炎症反应。由于已证实在AD脑中有PARP-1过度活化，我们检验了以下假设：PARP-1 -410和-1672多态性会因PARP-1基因的过表达，独立地或与促炎IL-1A -889多态性共同作用，使人们易患AD。因此，我们对263名西班牙AD患者和293名健康对照者进行了病例对照研究。PARP-1 -410和PARP-1 -1672单倍型与AD风险增加相关（整体单倍型关联p值=0.019），此外，PARP-1单倍型通过与IL-1A -889等位基因2相互作用增加了AD风险。
