Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Neurobiol Aging. 2009 Dec;30(12):2000-9. doi: 10.1016/j.neurobiolaging.2008.02.003. Epub 2008 Mar 24.
Genetic association of the dynamin binding protein gene (DNMBP) on chromosome 10 with late-onset Alzheimer's disease (AD) was reported among Japanese. Here, we assessed the genetic role of DNMBP in an extended Belgian AD group using a gene-wide association approach. A total of 18 SNPs across the DNMBP locus were genotyped in 555 late-onset AD patients and 638 healthy control individuals. Significant associations were observed for two SNPs (rs3740057 and rs10883421). Haplotype analysis identified association with haplotype blocks in the 3' region of DNMBP comprising rs2862919, rs11190302, rs10509739, rs2256700 and comprising rs3740057 and rs6584331. Stratification for APOE epsilon4 status showed that association was only present in the APOE epsilon4 negative subgroup. Sliding-window analyses provided further evidence for association with the 3'-end of DNMBP both for the total and for the APOE epsilon4 negative group. Taken together our findings underscore a role for DNMBP in the genetic risk for late-onset AD in the Belgian population.
DNMBP 基因（位于 10 号染色体上）与晚发性阿尔茨海默病（AD）的遗传关联在日本人群中已有报道。在此，我们采用全基因组关联分析方法，在一个扩展的比利时 AD 患者群体中评估了 DNMBP 的遗传作用。在 555 名晚发性 AD 患者和 638 名健康对照个体中，对 DNMBP 基因座上的 18 个 SNP 进行了基因分型。两个 SNP（rs3740057 和 rs10883421）存在显著关联。单体型分析确定了与 DNMBP 3'区域的单体型块相关，该区域包含 rs2862919、rs11190302、rs10509739、rs2256700 和包含 rs3740057 和 rs6584331。APOE ε4 状态分层显示，关联仅存在于 APOE ε4 阴性亚组中。滑动窗口分析为 DNMBP 的 3'端与总人群和 APOE ε4 阴性人群的关联提供了进一步的证据。综上所述，我们的研究结果强调了 DNMBP 在比利时人群中晚发性 AD 的遗传风险中的作用。
