Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4347158 | Neuroscience Letters | 2009 | 4 Pages |
Abstract
Amyloid β-peptide (Aβ) deposition in brain is important in the development of sporadic Alzheimer's disease (SAD) and Aβ is produced through sequential cleaving of amyloid precursor protein (APP) by β-secretase and γ-secrease. Anterior pharynx-defective-1 (APH-1) is an important subunit of the gamma-secretase complex, and its expression level was associated with the activity of γ-secrease. We hypothesized that alterations in the APH-1 promoter region might alter APH-1 expression and the activity of γ-secrease, thus be involved in the SAD process. In the present study, we sequenced APH-1a promoter region in 20 randomly selected controls and 20 SAD patients and detected two polymorphisms which were â980C/G (rs3754048) and â21C/A (rs2275780). Then, we investigated genotypes and allele of these two polymorphisms as well as apolipoprotein É4 (APOE É4) status in 256 SAD patients and 276 normal controls with restriction fragment length polymorphisms analysis and sequencing. Results showed the GG genotype and G allele of â980C/G polymorphism were more frequent in the SAD group than that in the controls not only in the whole subjects (genotype P = 0.038, allele P = 0.01 respectively) but also in the APOE É4 + subjects (genotype P = 0.048, allele P = 0.016 respectively). There was no statistical difference between SAD group and controls regarding to the frequency of alleles and genotypes of â21C/A whenever before or after stratification by APOE É4. Our results suggest that there is an association between â980C/G and the development of SAD in the Northern Han Chinese population and that allele G may interact synergistically with the APOE É4 allele to increase the risk of SAD.
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Authors
Yan Wang, Jianping Jia,