Back to Search
Start Over
Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease
- Source :
- Journal of neural transmission (Vienna, Austria : 1996). 115(11)
- Publication Year :
- 2008
-
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.
- Subjects :
- Male
Genotype
Taiwan
Gene Expression
Gene Frequency
Alzheimer Disease
Risk Factors
Amyloid precursor protein
Odds Ratio
Tumor Cells, Cultured
Humans
Allele
Promoter Regions, Genetic
Allele frequency
Endoplasmic Reticulum Chaperone BiP
Biological Psychiatry
Alleles
Heat-Shock Proteins
Aged
Polymorphism, Genetic
biology
Endoplasmic reticulum
Odds ratio
DNA
Molecular biology
Psychiatry and Mental health
Neurology
Chaperone (protein)
Unfolded protein response
biology.protein
Female
Neurology (clinical)
Molecular Chaperones
Subjects
Details
- ISSN :
- 03009564
- Volume :
- 115
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of neural transmission (Vienna, Austria : 1996)
- Accession number :
- edsair.doi.dedup.....e0a7164def755d2a127027d66f770d5f