Human Genetics

, Volume 114, Issue 3, pp 236–241

Analysis of heat-shock protein 70 gene polymorphisms and the risk of Parkinson’s disease

  • Yih-Ru Wu
  • Cheng-Kuang Wang
  • Chiung-Mei Chen
  • Yuying Hsu
  • Sih-Jing Lin
  • Yi-Ying Lin
  • Hon-Chung Fung
  • Kuo-Hsuan Chang
  • Guey-Jen Lee-Chen
Original Investigation

DOI: 10.1007/s00439-003-1050-1

Cite this article as:
Wu, YR., Wang, CK., Chen, CM. et al. Hum Genet (2004) 114: 236. doi:10.1007/s00439-003-1050-1

Abstract

Parkinson’s disease (PD) involves several genetic and environmental components. Heat-shock protein 70, a chaperone that is up-regulated in stress responses and that refolds protein, may be involved in the pathogenesis of PD. We have investigated the association of polymorphisms −110 A/C, +190 G/C, +1267 A/G, +2074 G/C, and +2437 G/C in the 5’ and coding regions of the HSP70-1, HSP70-2, and HSP70-hom genes with the risk of PD by screening DNA samples from 274 PD patients and 183 controls in assays based on the polymerase chain reaction. There was no statistically significant difference in genotype distribution between patients and controls for the three coding-region polymorphisms in HSP70-2 and HSP70-hom. However, for HSP70-1, the overall genotype distribution was significantly different at the −110 site (P=0.004) and tended to be different at the +190 site (P=0.012) between patients and controls. The frequencies of the −110 CC and +190 CC genotypes were significantly higher in PD patients than in controls (P=0.001 and 0.006, respectively). Both −110 CC (odds ratio: 2.91; 95% CI: 1.51–5.96; P=0.002) and +190 CC (odds ratio: 3.59; 95% CI: 1.53–9.88; P=0.006) genotypes were significantly associated with PD. Reporter constructs containing the −110 A allele cloned into a luciferase reporter plasmid drove marginally higher transcriptional activity of HSP70-1 compared with the −110 C allele in both control and heat-shocked IMR32 and 293 cells. Therefore, −110 A/C may be a functional polymorphism in the 5’ promoter region of HSP70-1 and may affect susceptibility to PD.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Yih-Ru Wu
    • 1
  • Cheng-Kuang Wang
    • 2
    • 3
  • Chiung-Mei Chen
    • 1
  • Yuying Hsu
    • 2
  • Sih-Jing Lin
    • 2
  • Yi-Ying Lin
    • 4
  • Hon-Chung Fung
    • 1
  • Kuo-Hsuan Chang
    • 1
  • Guey-Jen Lee-Chen
    • 2
  1. 1.Second Department of Neurology, Chang Gung Memorial Hospital and College of MedicineChang Gung UniversityTaipeiTaiwan
  2. 2.Department of Life ScienceNational Taiwan Normal UniversityTaipeiTaiwan
  3. 3.Jen-Teh Junior College of Medicine, Nursing and ManagementMiaoliTaiwan
  4. 4.School of Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan