Erschienen in:
01.11.2008 | Alzheimer's Disease and Related Disorders - Original Article
Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease
verfasst von:
W.-C. Hsu, H.-K. Wang, L.-C. Lee, H.-C. Fung, J.-C. Lin, H.-P. Hsu, Y.-R. Wu, L.-S. Ro, F.-J. Hu, Y.-T. Chang, G.-J. Lee-Chen, C.-M. Chen
Erschienen in:
Journal of Neural Transmission
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Ausgabe 11/2008
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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.