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 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.