Insulin-degrading enzyme and Alzheimer disease: A genetic association study in the Han Chinese

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 identi fied a possible role of IDE in the degradation of amyloid β protein and the intracellular amyloid precursor protein (APP) domain released by γ 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 4 status indicated that the association between IDE2 and AD was confined to APOE 4 carriers only. No association was found between all variants studied and AD within APOE 4 negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, over representation 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 4 in the risk to develop late onset sporadic AD. IDE might modify the effect of the APOE 4 risk factor in the Han Chinese population.