title: Genetic association of the presenilin-1 regulatory region with early-onset Alzheimer's disease in a population-based sample.
abstract: Genetic association has been reported between a di-allelic polymorphism in intron 8 of presenilin-1 (PSEN1) and Alzheimer's disease (AD) in some studies but not in others. In a population-based series of 102 patients with early onset AD and 118 community controls we examined whether polymorphisms in linkage disequilibrium with intron8 of PSEN1 may explain the association. In addition to the intron 8 polymorphism (P = 0.05), a promoter polymorphism (P = 0.03) and the simple tandem repeat (STR) polymorphism D14S1028 located upstream of PSEN1 (P = 0.04) were found to be marginally significantly associated to AD. When excluding PSEN1 mutation cases (n = 6), the intron 8 association was explained by linkage disequilibrium to the dominant PSEN1 mutations. In the non-mutation cases, the weak associations between the polymorphisms in the regulatory region remained. Our study suggests that a polymorphism/mutation in the promoter or regulatory region of PSEN1 rather than the polymorphism in intron 8 of PSEN1 is associated with early onset AD.
authors.affiliation: Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: M
authors.initials: M
authors.lastname: Cruts
authors.forename: J
authors.initials: J
authors.lastname: Theuns
authors.forename: G
authors.initials: G
authors.lastname: Van Gassen
authors.forename: H
authors.initials: H
authors.lastname: Backhovens
authors.forename: M
authors.initials: M
authors.lastname: van den Broeck
authors.forename: A
authors.initials: A
authors.lastname: Wehnert
authors.forename: S
authors.initials: S
authors.lastname: Serneels
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005809:Genes, Regulator / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D053764:Presenilin-1; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1