| Title | The -48 C/T polymorphism in the presenilin 1 promoter is associated with an increased risk of developing Alzheimer's disease and an increased Abeta load in brain. | | Author(s) | Lambert JC, Mann DM, Harris JM, Chartier-Harlin MC, Cumming A, Coates J, Lemmon H, StClair D, Iwatsubo T, Lendon C | | Institution | Molecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK. | | Source | J Med Genet 2001 Jun; 38(6):353-5. | | MeSH | Age of Onset
Aged
Alzheimer Disease
Amyloid beta-Protein
Brain
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Male
Membrane Proteins
Polymorphism, Single Nucleotide
Presenilin-1
Promoter Regions (Genetics)
| | Abstract | Mutations in the presenilin 1 gene (PS1) account for the majority of early onset, familial, autosomal dominant forms of Alzheimer's disease (AD), whereas its role in other late onset forms of AD remains unclear. A -48 C/T polymorphism in the PS1 promoter has been associated with an increased genetic risk in early onset complex AD and moreover has been shown to influence the expression of the PS1 gene. This raises the possibility that previous conflicting findings from association studies with homozygosity for the PS1 intron 8 polymorphism might be the result of linkage disequilibrium with the -48 CC genotype. Here we provide further evidence of increased risk of AD associated with homozygosity for the -48 CC genotype (odds ratio=1.6). We also report a phenotypic correlation with Abeta(40), Abeta(42(43)), and total Abeta load in AD brains. The -48 CC genotype was associated with 47% greater total Abeta load (p<0.003) compared to CT + TT genotype bearers. These results suggest that the -48 C/T polymorphism in the PS1 promoter may increase the risk of AD, perhaps by altering PS1 gene expression and thereby influencing Abeta load. | | Language | eng | | Pub Type(s) | Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
| | PubMed ID | 11389157 |
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