Association between glycogen synthase kinase-3β genetic polymorphism and late-onset Alzheimer's disease
Association between glycogen synthase kinase-3β genetic polymorphism and late-onset Alzheimer's disease
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DOI：
10.1159/000091044
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
Combarros, O
中科院分区：
文献类型：
--
作者：
Mateo, I;Infante, J;Combarros, O
异常磷酸化的tau蛋白是阿尔茨海默病（AD）大脑中神经原纤维缠结的主要成分。糖原合成酶激酶-3 β (GSK-3 β)磷酸化tau蛋白，GSK-3 β表达增加与神经原纤维缠结有关。Saitohin （STH）是最近发现的一种与tau蛋白具有相同组织表达模式的蛋白，先前在西班牙人群中的证据表明，Saitohin基因密码子7 （Q7R）的多态性与晚发性AD有关。由于GSK-3 β和STH都与tau蛋白有关，我们通过独立作用或通过与STH （Q7R）多态性的相互作用，对来自西班牙的333名散发性AD患者和307名对照受试者进行了GSK-3 β基因启动子区域（-50）多态性与AD之间的关系进行了研究。目前的研究显示GSK-3 β (-50) TT基因型与迟发性（72岁以后）AD的风险增加相关（OR 1.99, p = 0.003）。我们的研究结果表明，GSK-3 β(-50)和STH （Q7R）多态性都增加了迟发性AD（受试者bb - 72岁）的风险，尽管它们似乎是独立的，因此不会协同作用。
Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylates tau protein, and increased GSK-3 beta expression has been associated with neurofibrillary tangles. Saitohin (STH) is a recently identified protein that shares tissue expression pattern with tau, and previous evidence in the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH gene was associated with late-onset AD. Since both GSK-3 beta and STH are related to tau, we examined the association between a polymorphism in the promoter region (-50) of the GSK-3 beta gene and AD, either through an independent effect or through interaction with the STH (Q7R) polymorphism, in a well-defined group of 333 sporadic AD patients and 307 control subjects from Spain. The current study reveals that GSK-3 beta (-50) TT genotype is associated with an increased risk (OR 1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results indicate that both the GSK-3 beta (-50) and STH (Q7R) polymorphisms increase the risk of late-onset ( subjects > 72 years) AD, although they appear to be independent and thus not to interact synergistically.