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日本人群中Akt1基因多态性与阿尔茨海默病的遗传关联

Genetic Association between Akt1 Polymorphisms and Alzheimer's Disease in a Japanese Population.

作者信息

Shibata Nobuto, Ohnuma Tohru, Kuerban Bolati, Komatsu Miwa, Baba Hajime, Arai Heii

机构信息

Department of Psychiatry, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

出版信息

Int J Alzheimers Dis. 2011;2011:762471. doi: 10.4061/2011/762471. Epub 2011 Jul 14.

Abstract

A recent paper reported that Aβ oligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)-Akt-mTOR signaling pathway. Intraneuronal Aβ, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD.

摘要

最近一篇论文报道,β淀粉样蛋白(Aβ)寡聚体通过磷脂酰肌醇-3-羟基激酶(PI3K)-蛋白激酶B(Akt)-哺乳动物雷帕霉素靶蛋白(mTOR)信号通路导致神经元细胞死亡。神经元内Aβ是阿尔茨海默病(AD)的主要病理学发现,也被认为可抑制Akt的激活。本研究旨在调查Akt1基因的单核苷酸多态性(SNP)是否与AD相关。采用病例对照研究设计分析了使用TaqMan技术进行基因分型的SNP。我们的病例对照数据集包括180例AD患者和130例年龄匹配的对照。尽管有两个SNP显示出表面上的阳性,但哈迪-温伯格平衡(HWE)检验和连锁不平衡(LD)分析表明该基因的遗传区域具有高度多态性。我们未能检测到Akt1多态性、载脂蛋白E(APOE)和AD之间的任何协同关联。需要进一步的遗传学研究来阐明Akt1与AD之间的关系。

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