Li Yonghong, Grupe Andrew, Rowland Charles, Holmans Peter, Segurado Ricardo, Abraham Richard, Jones Lesley, Catanese Joseph, Ross David, Mayo Kevin, Martinez Maribel, Hollingworth Paul, Goate Alison, Cairns Nigel J, Racette Brad A, Perlmutter Joel S, O'Donovan Michael C, Morris John C, Brayne Carol, Rubinsztein David C, Lovestone Simon, Thal Leon J, Owen Michael J, Williams Julie
Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA.
Hum Mol Genet. 2008 Mar 1;17(5):759-67. doi: 10.1093/hmg/ddm348. Epub 2007 Dec 6.
Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N = 3521, P = 5.38x10(-6), odds ratio (OR) = 1.38 (1.20-1.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N = 1464, P = 0.0145, OR =1.31 (1.05-1.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.
迟发性阿尔茨海默病（LOAD）和帕金森病（PD）是最常见的神经退行性疾病，已知这两种疾病的易感性均受基因影响。我们通过开展一项大规模、多层次的关联研究，对4692个单核苷酸多态性（SNP）进行检测，旨在鉴定LOAD的新型易感基因。我们在NEDD9基因（神经前体细胞表达，发育过程中下调）的一个假定转录因子结合位点内鉴定出一个SNP，该SNP在五分之四的LOAD样本中显示出与疾病风险存在关联的有力证据【N = 3521，P = 5.38×10⁻⁶，比值比（OR）= 1.38（1.20 - 1.59）】，此外，我们在两个PD样本组中也观察到了类似的关联模式【N = 1464，P = 0.0145，OR = 1.31（1.05 - 1.62）】。在探索这种关联的潜在机制时，我们观察到在阿尔茨海默病患者的海马体中，NEDD9和APOE的表达呈强烈负相关。这些数据表明NEDD9是LOAD以及可能是PD的新型易感基因。
