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Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzyme

Lookup NU author(s): Professor Ian McKeith, Emeritus Professor Robert Perry, Dr Christopher Morris

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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 Aβ. 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. © 2005 Wiley-Liss, Inc.

Publication metadata

Author(s): Nowotny P, Hinrichs AL, Smemo S, Kauwe JSK, Maxwell T, Holmans P, Hamshere M, Turic D, Jehu L, Hollingworth P, Moore P, Bryden L, Myers A, Doil LM, Tacey KM, Gibson AM, McKeith IG, Perry RH, Morris CM, Thal L, Morris JC, O'Donovan MC, Lovestone S, Grupe A, Hardy J, Owen MJ, Williams J, Goate A

Publication type: Article

Publication status: Published

Journal: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Year: 2005

Volume: 136

Issue: 1

Pages: 62-68

ISSN (print): 1552-4841

ISSN (electronic): 1552-485X

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1002/ajmg.b.30186

DOI: 10.1002/ajmg.b.30186

PubMed id: 15858813

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