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中国汉族人群中低密度脂蛋白受体相关蛋白基因多态性与阿尔茨海默病的遗传关联。

Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population.

作者信息

Zhou Yong-Tao, Zhang Zhen-Xin, Chan Piu, He Xiao-Ming, Tang Mou-Ni, Wu Cheng-Bin, Hong Zhen

机构信息

Department of Neurology and Neurobiology, Key Laboratory of Neurodegenerative Diseases for Ministry of Education, Beijing Institute of Geriatrics and Xuanwu Hospital of Capital University of Medical Sciences, 100053 Beijing, China.

出版信息

Neurosci Lett. 2008 Oct 17;444(1):109-11. doi: 10.1016/j.neulet.2008.07.093. Epub 2008 Aug 8.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population.

摘要

阿尔茨海默病(AD)是老年人中最常见的神经退行性疾病。低密度脂蛋白受体相关蛋白(LRP)作为载脂蛋白E(APOE)、淀粉样前体蛋白(APP)和α2巨球蛋白(α2-M)的受体,维持着β淀粉样蛋白(Aβ)清除的降解与生成之间的平衡。其基因曾被定义为AD的候选基因,但结果并不具有普遍性。在中国汉族人群中招募了496例AD患者和478名对照,采用实时聚合酶链反应(PCR)检测LRP C766T的多态性。进行多因素逻辑回归、卡方检验和生存分析以探讨其关联性。病例组和对照组之间LRP基因型和等位基因的分布存在显著差异,T等位基因可降低患AD的风险(CT基因型的比值比:0.57;95%可信区间:0.38 - 0.85,P = 0.003;T等位基因的比值比:0.57;95%可信区间:0.39 - 0.83,P = 0.003)。与CC基因型携带者相比,TT基因型携带者患AD的时间要晚5年,但生存分析并不符合这一结果(LRP TT与CT和CC的对数秩检验χ2 = 2.71,P = 0.26)。按简易精神状态检查表(MMSE)分层的不同严重程度患者中,LRP C766T基因型和等位基因的分布也存在差异(P = 0.26)。我们的数据表明,LRP C766T的多态性与AD密切相关,在中国汉族人群中T等位基因可能是AD的一个保护因素。

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