Promoter polymorphisms which modulate insulin degrading enzyme expression may increase susceptibility to Alzheimer's disease

作者：Zuo Xiumei; Jia Jianping^*

来源：Brain Research, 2009, 1249: 1-8.

DOI：10.1016/j.brainres.2008.10.034

• Alzheimer's disease
• IDE
• Promoter
• Polymorphism

Cerebral accumulation of amyloid beta protein (A beta) is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Insulin degrading enzyme (IDE) is involved in A beta degradation, therefore the gene encoding for insulin degrading enzyme is one of the candidate genes risky for AD. In Chinese Han populations we found three polymorphisms in IDE promoter: -1002T/G (rs3758505), -179T/C (rs4646953) and -51C/T (rs4646954). The -1002T and -51C alleles were over-represented in 357 sporadic AD (SAD) patients when compared to those in 331 healthy individuals. Furthermore, -1002T/G and -51C/T were in strong linkage disequilibrium and they constructed a relatively risky -1002T/-51C and a relatively protective -1002G/-51T. Luciferase reporter assay indicated -1002T/-51C had lower transcriptional activity than -1002G/-51T. A more marked increase in -1002T/-51C transcriptional activity was seen when under A beta(25-35) and serum deprivation treatment. The present study provides evidence that IDE promoter polymorphisms that significantly decrease IDE expression levels are associated with development of SAD.

• 出版日期2009-1-16
• 单位首都医科大学