Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease

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

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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.

Original languageEnglish
Pages (from-to)1537-1543
Number of pages7
JournalJournal of Neural Transmission
Volume115
Issue number11
DOIs
Publication statusPublished - 2008 Nov 1

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Keywords

  • Alzheimer's disease
  • Disease association
  • HSPA5/GRP78
  • Promoter SNPs

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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. (2008). Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease. Journal of Neural Transmission, 115(11), 1537-1543. https://doi.org/10.1007/s00702-008-0117-5