title: Amyloid precursor protein gene (APP) variation in late-onset Alzheimer's disease.
abstract: Mutations in the beta-amyloid precursor protein gene (APP) have been found in familial early-onset Alzheímer's disease (AD). DNA variants at several genes have been linked to the risk of developing the most common late-onset form of AD (LOAD). A few studies analyzed the contribution of APP variants to LOAD, with negative or conflicting results. We determined the variation in the 18 APP exons and flanking intronic sequences in a total of 350 LOAD patients from Spain. A total of 13 nucleotide changes were found and 6 were new and not found among 340 healthy controls, including the only missense change (D243N). The in silico analysis suggested that none of them would have an effect on pre-mRNA splicing or protein folding (D243N). Patients and controls were also genotyped for three APP promoter polymorphisms, and none of them was significantly associated with LOAD. We concluded that APP variants would not contribute to the risk of developing LOAD in our population.
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Miar
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: María T
authors.initials: MT
authors.lastname: Calatayud
authors.forename: Manuel
authors.initials: M
authors.lastname: Menéndez
authors.forename: Germán
authors.initials: G
authors.lastname: Morís
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013030:Spain
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E