title: Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzyme.
abstract: Linkage studies have suggested there is a susceptibility gene for late onset Alzheimer's disease (LOAD) in a broad region of chromosome 10. A strong positional and biological candidate is the gene encoding the insulin-degrading enzyme (IDE), a protease involved in the catabolism of Abeta. However, previous association studies have produced inconsistent results. To systematically evaluate the role of variation in IDE in the risk for LOAD, we genotyped 18 SNPs spanning a 276 kb region in and around IDE, including three "tagging" SNPs identified in an earlier study. We used four case-control series with a total of 1,217 cases and 1,257 controls. One SNP (IDE_7) showed association in two samples (P-value = 0.0066, and P = 0.026, respectively), but this result was not replicated in the other two series. None of the other SNPs showed association with LOAD in any of the tested samples. Haplotypes, constructed from the three tagging SNPs, showed no globally significant association. In the UK2 series, the CTA haplotype was over-represented in cases (P = 0.046), and in the combined data set, the CCG haplotype was more frequent in controls (P = 0.015). However, these weak associations observed in our series were in the opposite direction to the results in previous studies. Although our results are not universally negative, we were unable to replicate the results of previous studies and conclude that common variants or haplotypes of these variants in IDE are not major risk factors for LOAD.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Nowotny
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Hinrichs
authors.forename: Scott
authors.initials: S
authors.lastname: Smemo
authors.forename: John S K
authors.initials: JS
authors.lastname: Kauwe
authors.forename: Taylor
authors.initials: T
authors.lastname: Maxwell
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Marian
authors.initials: M
authors.lastname: Hamshere
authors.forename: Dragana
authors.initials: D
authors.lastname: Turic
authors.forename: Luke
authors.initials: L
authors.lastname: Jehu
authors.forename: Paul
authors.initials: P
authors.lastname: Hollingworth
authors.forename: Pamela
authors.initials: P
authors.lastname: Moore
authors.forename: Leslie
authors.initials: L
authors.lastname: Bryden
authors.forename: Amanda
authors.initials: A
authors.lastname: Myers
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Doil
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Tacey
authors.forename: Alison M
authors.initials: AM
authors.lastname: Gibson
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: Robert H
authors.initials: RH
authors.lastname: Perry
authors.forename: Chris M
authors.initials: CM
authors.lastname: Morris
authors.forename: Leon
authors.initials: L
authors.lastname: Thal
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D005819:Genetic Markers; D007339:Insulysin