阿尔茨海默病中α-T连环蛋白基因（VR22）与载脂蛋白E的相互作用。
Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.
作者信息
Martin E R, Bronson P G, Li Y-J, Wall N, Chung R-H, Schmechel D E, Small G, Xu P-T, Bartlett J, Schnetz-Boutaud N, Haines J L, Gilbert J R, Pericak-Vance M A
出版信息
J Med Genet. 2005 Oct;42(10):787-92. doi: 10.1136/jmg.2004.029553.
BACKGROUND
APOE is the only gene that has been consistently replicated as a risk factor for late onset Alzheimer's disease. Several recent studies have identified linkage to chromosome 10 for both risk and age of onset, suggesting that this region harbours genes that influence the development of the disease. A recent study reported association between single nucleotide polymorphisms (SNPs) in the VR22 gene (CTNNA3) on chromosome 10 and plasma levels of Abeta42, an endophenotype related to Alzheimer's disease.
OBJECTIVE
To assess whether polymorphisms in the VR22 gene are associated with Alzheimer's disease in a large sample of Alzheimer's disease families and an independent set of unrelated cases and controls.
RESULTS
Several SNPs showed association in either the family based or case-control analyses (p<0.05). The most consistent findings were with SNP6, for which there was significant evidence of association in both the families and the unrelated cases and controls. Furthermore, there was evidence of significant interaction between APOE-4 and two of the VR22 SNPs, with the strongest evidence of association being concentrated in individuals carrying APOE-4.
CONCLUSIONS
This study suggests that VR22 or a nearby gene influences susceptibility to Alzheimer's disease, and the effect is dependent on APOE status.
背景
载脂蛋白E（APOE）是唯一一个一直被确认为晚发型阿尔茨海默病风险因素的基因。最近的几项研究已确定10号染色体与发病风险和发病年龄存在连锁关系，这表明该区域存在影响该病发展的基因。最近一项研究报告称，10号染色体上VR22基因（CTNNA3）中的单核苷酸多态性（SNP）与β淀粉样蛋白42（Abeta42）的血浆水平相关，Abeta42是一种与阿尔茨海默病相关的内表型。
目的
在大量阿尔茨海默病家族样本以及一组独立的非相关病例和对照中，评估VR22基因中的多态性是否与阿尔茨海默病相关。
结果
在基于家系的分析或病例对照分析中，有几个单核苷酸多态性显示出相关性（p<0.05）。最一致的发现是与SNP6相关，在家族以及非相关病例和对照中均有显著的相关证据。此外，有证据表明APOE-4与两个VR22单核苷酸多态性之间存在显著相互作用，最强的相关证据集中在携带APOE-4的个体中。
结论
本研究表明，VR22或其附近的基因影响阿尔茨海默病的易感性，且这种影响取决于APOE状态。
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