title: Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease.
abstract: We recently reported that a linkage disequilibrium (LD) block on chromosome 10q encompassing the gene encoding insulin-degrading enzyme ( IDE) harbors sequence variants that associate with Alzheimer disease (AD). Evidence also indicated effects upon a number of quantitative indices of AD severity, including age-at-onset (AAO). Since linkage of this immediate region to AAO has been shown in both AD and Parkinson disease (PD), we have explored the possibility that polymorphism within this LD block might also influence PD. Utilizing single nucleotide polymorphisms that delineate common haplotypes from this region, we observed significant evidence of association with AAO in an Australian PD case-control sample. Analyses were complemented with AAO data from two independent Swedish AD case samples, for which previously reported findings were replicated. Results were consistent between AD and PD, suggesting the presence of equivalent detrimental and protective alleles. These data highlight a genomic region in the proximity of IDE that may contribute to AD and PD in a similar manner.
authors.affiliation: Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mia E-L
authors.initials: ME
authors.lastname: Blomqvist
authors.forename: Peter A
authors.initials: PA
authors.lastname: Silburn
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brookes
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Prince
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D005260:Female; D005838:Genotype; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*
chemical_list: D007339:Insulysin