Suppr超能文献

启动子多态性可调节 BACE1 的表达,与散发性阿尔茨海默病相关。

Promoter polymorphisms which modulate BACE1 expression are associated with sporadic Alzheimer's disease.

机构信息

Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):159-66. doi: 10.1002/ajmg.b.30968.

Abstract

Beta-site APP-cleaving enzyme 1 (BACE1) gene has been suggested as a candidate gene for Alzheimer's disease (AD). However, little is known regarding the effects of polymorphisms in regulatory sequences of BACE1 on AD susceptibility. To evaluate the relationship between polymorphisms in the BACE1 promoter and sporadic AD (SAD) genetically and functionally, we performed a case-control study (429 cases and 346 controls of Han Chinese descent) and functional characterization of the polymorphisms in vitro using luciferase assay and electrophoretic mobility shift assay (EMSA). Two polymorphisms (-918G/A, rs4938369; -2014T/C, rs3017608) were identified in the BACE1 promoter. The results showed that the -918G/A polymorphism was associated with SAD and the -918GG carriers had a 1.67-fold higher risk for SAD than the carriers with -918AA and GA genotypes (OR = 1.667, 95% CI = 1.087-2.556, P = 0.019). The haplotype -918G/-2014T may be a possible risk factor for SAD (P = 0.016). Luciferase reporter assays showed the -918G allele and its resultant haplotype -918G/-2014T induced an increase of transcriptional activity. A more marked increase in -918G/-2014T transcriptional activity was seen when under hypoxia treatment. EMSA indicated that the -918G allele bound nuclear factors more strongly than -918A allele did. Our findings suggest that the BACE1 promoter polymorphisms which regulate BACE1 expression may contribute to SAD susceptibility. Further independent studies are required to verify our findings.

摘要

β 位淀粉样前体蛋白裂解酶 1(BACE1)基因被认为是阿尔茨海默病(AD)的候选基因。然而,关于 BACE1 调控序列多态性对 AD 易感性的影响知之甚少。为了评估 BACE1 启动子多态性与散发性 AD(SAD)之间的遗传和功能关系,我们进行了病例对照研究(汉族 429 例病例和 346 例对照),并使用荧光素酶报告基因检测和电泳迁移率变动分析(EMSA)对多态性进行了体外功能表征。在 BACE1 启动子中发现了两个多态性(-918G/A,rs4938369;-2014T/C,rs3017608)。结果表明,-918G/A 多态性与 SAD 相关,与 -918AA 和 GA 基因型携带者相比,-918GG 携带者发生 SAD 的风险增加 1.67 倍(OR=1.667,95%CI=1.087-2.556,P=0.019)。-918G/-2014T 单体型可能是 SAD 的一个潜在危险因素(P=0.016)。荧光素酶报告基因检测显示,-918G 等位基因及其产生的单体型 -918G/-2014T 可诱导转录活性增加。在缺氧处理下,-918G/-2014T 转录活性的增加更为显著。EMSA 表明,-918G 等位基因与核因子的结合能力强于-918A 等位基因。我们的研究结果表明,调节 BACE1 表达的 BACE1 启动子多态性可能与 SAD 的易感性有关。需要进一步的独立研究来验证我们的发现。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验