Insulin-degrading enzyme and Alzheimer disease - A genetic association study in the Han Chinese
Insulin-degrading enzyme and Alzheimer disease - A genetic association study in the Han Chinese
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DOI：
10.1212/01.wnl.0000129987.70037.db
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发表时间：
2004-07-27
期刊：
影响因子：
9.9
通讯作者：
He, L
中科院分区：
文献类型：
--
作者：
Bian, L;Yang, JD;He, L
背景：胰岛素降解酶（IDE）基因代表了迟发性阿尔茨海默病（LOAD）易感性的一个强有力的位置和生物学候选基因。 IDE 位于染色体 10q23.3 上，靠近 LOAD 连锁区域。此外，许多研究已经确定 IDE 在β-淀粉样蛋白和由 γ-分泌酶处理释放的细胞内淀粉样前体蛋白 (APP) 结构域的降解中可能发挥的作用。目的：探讨汉族人IDE与AD的关系。方法：使用年龄、性别和种族背景良好匹配的 210 名 LOAD 患者和 200 名对照受试者群体，分析了四种 IDE 多态性（三种位于 5'-非翻译区，一种位于内含子 21）。结果：在研究的四个多态性中，只有单核苷酸多态性 (SNP) IDE2 的 C 等位基因显示与 AD 相关 (p = 0.005)。按 APOE epsilon4 状态对数据进行分层表明 IDE2 和 AD 之间的关联仅限于 APOE epsilon4 携带者。在 APOE epsilon4 阴性受试者中，所有研究的变异与 AD 之间没有发现关联。 AD 患者和对照受试者之间的整体单倍型频率显示出显着差异。此外，还发现 AD 组中 GCTG 单倍型的比例过高。它可能是 AD 的风险单倍型。结论：这些结果表明 IDE 和 APOE epsilon4 之间可能存在协同相互作用，以降低晚发散发性 AD 的风险。 IDE 可能会改变 APOE epsilon4 危险因素对中国汉族人群的影响。
Background: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease ( LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid beta-protein and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. Objective: To examine the association of IDE with AD in the Han Chinese. Methods: Four IDE polymorphisms ( three in 5'-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. Results: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD ( p = 0.005). Stratification of the data by APOE epsilon4 status indicated that the association between IDE2 and AD was confined to APOE epsilon4 carriers only. No association was found between all variants studied and AD within APOE epsilon4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. Conclusions: These results suggest a possible synergic interaction between IDE and APOE epsilon4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE epsilon4 risk factor in the Han Chinese population.