Journal of Neural Transmission

, 115:1537

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
Alzheimer's Disease and Related Disorders - Original Article

DOI: 10.1007/s00702-008-0117-5

Cite this article as:
Hsu, WC., Wang, HK., Lee, LC. et al. J Neural Transm (2008) 115: 1537. doi:10.1007/s00702-008-0117-5

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.

Keywords

Alzheimer’s disease HSPA5/GRP78 Promoter SNPs Disease association 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • W.-C. Hsu
    • 1
  • H.-K. Wang
    • 2
  • L.-C. Lee
    • 2
  • H.-C. Fung
    • 1
  • J.-C. Lin
    • 1
    • 3
  • H.-P. Hsu
    • 1
    • 3
  • Y.-R. Wu
    • 1
  • L.-S. Ro
    • 1
  • F.-J. Hu
    • 2
  • Y.-T. Chang
    • 2
  • G.-J. Lee-Chen
    • 2
  • C.-M. Chen
    • 1
  1. 1.Department of Neurology, Chang Gung Memorial HospitalChang Gung University College of MedicineTaipeiTaiwan
  2. 2.Department of Life ScienceNational Taiwan Normal UniversityTaipeiTaiwan
  3. 3.Department of NeurologySt Paul HospitalTaoyuanTaiwan