Positive association between risk for late-onset Alzheimer disease and genetic variation in IDE

Björk, Behnosh F.; Katzov, Hagit; Kehoe, Patrick; Fratiglioni, Laura; Winblad, Bengt; Prince, Jonathan A.; Graff, Caroline

doi:10.1016/j.neurobiolaging.2006.06.017

« Previous Next »Neurobiology of Aging
Volume 28, Issue 9 , Pages 1374-1380, September 2007

Positive association between risk for late-onset Alzheimer disease and genetic variation in IDE

Behnosh F. Björk
- Karolinska Institutet, Department NVS, Division of KI-Alzheimer Disease Research Center, SE-141 57 Huddinge, Sweden
Hagit Katzov
- Karolinska Institutet, Centre for Genomics and Bioinformatics (CGB), SE-171 77 Stockholm, Sweden
Patrick Kehoe
- Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK
Laura Fratiglioni
- Karolinska Institutet, Department Neurotec, Division of Geriatric Epidemiology, SE-113 82 Stockholm, Sweden
Bengt Winblad
- Karolinska Institutet, Department NVS, Division of KI-Alzheimer Disease Research Center, SE-141 57 Huddinge, Sweden
Jonathan A. Prince
- Karolinska Institutet, Centre for Genomics and Bioinformatics (CGB), SE-171 77 Stockholm, Sweden
Caroline Graff
- Karolinska Institutet, Department NVS, Division of KI-Alzheimer Disease Research Center, SE-141 57 Huddinge, Sweden
- Corresponding author. Tel.: +46 8 585 83619; fax: +46 8 585 83610.

Received 9 December 2005; received in revised form 12 June 2006; accepted 19 June 2006. published online 02 August 2006.

Abstract

Insulin degrading enzyme (IDE) is one of the principal proteases involved in the degradation of the β-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using four SNPs in the 276-kb haplotype block in and around IDE (IDE_7, IDE_9, IDE_14 and HHEX_23) in a previously unpublished Swedish and a UK case–control series, and combined our data with a previously reported Swedish case–control sample set from Prince et al., 2003.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.