title: Positive association between risk for late-onset Alzheimer disease and genetic variation in IDE.
abstract: Insulin degrading enzyme (IDE) is one of the principal proteases involved in the degradation of the beta-amyloid peptide, which is the major constituent of senile plaques in Alzheimer's disease (AD) brains. Previous association studies between AD and IDE have produced inconsistent results which may be indicative of a need for larger case-control series to identify what may be a relatively small effect size. Thus, we performed a large association study using four SNPs in the 276-kb haplotype block in and around IDE (IDE_7, IDE_9, IDE_14 and HHEX_23) in a previously unpublished Swedish and a UK case-control series, and combined our data with a previously reported Swedish case-control sample set from Prince et al., 2003. The combined genotype data from 1269 late-onset AD cases and 980 controls yielded a significant association to IDE_9 located in the 3'-end of the IDE gene after conservative multiple testing Bonferroni correction (p=0.005). The effect seemed to predominate in male cases. However, we did not observe a globally significant association to haplotypes generated from three "tag" SNPs. These findings indicate a role for IDE in AD, and provide models that may improve chances of further independent replication.
authors.affiliation: Karolinska Institutet, Department NVS, Division of KI-Alzheimer Disease Research Center, SE-141 57 Huddinge, Sweden.
authors.forename: Behnosh F
authors.initials: BF
authors.lastname: Björk
authors.forename: Hagit
authors.initials: H
authors.lastname: Katzov
authors.forename: Patrick
authors.initials: P
authors.lastname: Kehoe
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Prince
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
chemical_list: D053327:Apolipoprotein E4; D007339:Insulysin