title: No association between an intronic polymorphism in the presenilin-1 gene and Alzheimer's disease.
abstract: Mutations in the presenilin-1 (PS-1) gene are believed to be responsible for the majority of familial early-onset Alzheimer's disease (AD). The finding of an intronic polymorphism in the PS-1 gene prompted an investigation into its relevance in AD. An association between homozygosity for the most common allele (allele 1) in this intronic polymorphism and late-onset AD has been shown and has been confirmed by others though some studies do not support these findings. We genotyped a large series of sporadic AD cases (n = 120) and age-matched controls (n = 108) for this intronic polymorphism. We then compared both the frequency of allele 1 and allele 1 homozygosity between the AD group as a whole and in early-onset (n = 26) and late-onset (n = 94) groups with age-matched control groups (n = 29 and n = 79, respectively). No increase in the frequency or homozygosity of allele 1 in either the AD group as a whole, or when divided into late- and early-onset cases was found. Increases in the frequency of allele 1 homozygotes and in the number of non-apolipoprotein E epsilon4 carrying allele 1 homozygotes/heterozygotes was demonstrated in the early-onset AD cases although these values did not reach significance. We conclude that there is no relationship between this intronic polymorphism in the PS-1 gene and AD in the homogenous population genotyped in this study.
authors.affiliation: Medical Research Council Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK. a.b.singleton@ncl.ac.uk
authors.forename: A B
authors.initials: AB
authors.lastname: Singleton
authors.forename: H
authors.initials: H
authors.lastname: Lamb
authors.forename: A
authors.initials: A
authors.lastname: Leake
authors.forename: I G
authors.initials: IG
authors.lastname: McKeith
authors.forename: R H
authors.initials: RH
authors.lastname: Perry
authors.forename: C M
authors.initials: CM
authors.lastname: Morris
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1