Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
Dement Geriatr Cogn Disord. 2009;28(4):325-9. doi: 10.1159/000251194. Epub 2009 Oct 22.
BACKGROUND/AIMS: A recent paper reported that the TAR-DNA binding protein (TDP-43) is the disease protein in amyotrophic lateral sclerosis and frontotemporal lobar dementia with ubiquitin-positive inclusions. In addition, it has been shown that TDP-43 may play a role in the pathogenesis of Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the TDP-43 gene are associated with AD.
Eight SNPs, genotyped using TaqMan technology, were analyzed using a case-control study design including a haplotype analysis. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consists of 181 AD patients and 130 age-matched controls.
Although none of the SNPs showed statistically significant association, we identified an association between a specific haplotype (G-A-A-G) of the TDP-43 gene and risk for AD. We could not confirm any synergetic association between the SNPs and APO E in our AD patients. Despite the relatively small sample size, our results indicate a possible genetic association between TDP- 43 and AD.
Further genetic studies are needed to clarify the relationship between the TDP-43 gene and AD.
背景/目的：最近的一篇论文报道称，TAR-DNA 结合蛋白（TDP-43）是肌萎缩侧索硬化症和额颞叶痴呆伴泛素阳性包涵体的疾病蛋白。此外，已有研究表明 TDP-43 可能在阿尔茨海默病（AD）的发病机制中发挥作用。本研究旨在探讨 TDP-43 基因的单核苷酸多态性（SNPs）是否与 AD 相关。
采用 TaqMan 技术对 8 个 SNPs 进行基因分型，采用病例对照研究设计进行分析，包括单倍型分析。此外，还对根据载脂蛋白 E（APO E）状态进行分组的病例进行了分析。我们的病例对照数据集包括 181 名 AD 患者和 130 名年龄匹配的对照。
虽然没有一个 SNP 显示出统计学上的显著关联，但我们发现 TDP-43 基因的特定单倍型（G-A-A-G）与 AD 的风险之间存在关联。我们不能确认我们的 AD 患者中 SNP 和 APO E 之间存在任何协同关联。尽管样本量相对较小，但我们的结果表明 TDP-43 与 AD 之间可能存在遗传关联。
需要进一步的遗传研究来阐明 TDP-43 基因与 AD 之间的关系。
