We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease.
- Authors
Hsu, W-C; Wang, H-K; Lee, L-C; Fung, H-C; Lin, J-C; Hsu, H-P; Wu, Y-R; Ro, L-S; Hu, F-J; Chang, Y-T; Lee-Chen, G-J; Chen, C-M
- Abstract
Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer's disease (AD) could arise from dysfunction of the ER. Through a case-control study and an expression assay, we investigated the association of HSPA5 -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked -415 G/A and -180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for -415 AA/-180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18-0.75, P = 0.007] and -415 A/-180 G allele (OR = 0.69, 95% CI = 0.51-0.91, P = 0.009). The HSPA5 transcriptional activity of the -415 A/-180 G allele was significantly lower than that of the -415 G/-180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 -415 A/-180 G allele in Taiwanese AD susceptibility.
- Publication
Journal of neural transmission (Vienna, Austria : 1996), 2008, Vol 115, Issue 11, p1537
- ISSN
0300-9564
- Publication type
Journal Article
- DOI
10.1007/s00702-008-0117-5