Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease.
J Neural Transm (Vienna)
; 115(11): 1537-43, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-18781276
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Chaperonas Moleculares
/
Doença de Alzheimer
/
Proteínas de Choque Térmico
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Neural Transm (Vienna)
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Taiwan