Human Genetics

, Volume 118, Issue 3, pp 484–488

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association

  • E. K. Tan
  • K. Y. Puong
  • D. K. Y. Chan
  • K. Yew
  • S. Fook-Chong
  • H. Shen
  • P. W. Ng
  • J. Woo
  • Y. Yuen
  • R. Pavanni
  • M. C. Wong
  • K. Puvan
  • Y. Zhao
Original Investigation

DOI: 10.1007/s00439-005-0038-4

Cite this article as:
Tan, E.K., Puong, K.Y., Chan, D.K.Y. et al. Hum Genet (2005) 118: 484. doi:10.1007/s00439-005-0038-4

Abstract

We provided data to show that the transcriptional activity of wildtype −258T in the parkin promoter region was significantly higher than the −258G variant in human cell lines. The transcriptional activity of wildtype −258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the −258G variant. The transcriptional upregulation was significantly higher for wildtype −258T compared to −258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.

Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter −258G variant was associated with an increased risk of sporadic Parkinson’s disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the −258G variant may have a higher risk of developing PD.

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • E. K. Tan
    • 1
    • 4
    • 5
  • K. Y. Puong
    • 2
  • D. K. Y. Chan
    • 6
  • K. Yew
    • 1
  • S. Fook-Chong
    • 2
  • H. Shen
    • 1
    • 5
  • P. W. Ng
    • 7
  • J. Woo
    • 8
  • Y. Yuen
    • 3
  • R. Pavanni
    • 1
    • 4
    • 5
  • M. C. Wong
    • 1
    • 4
    • 5
  • K. Puvan
    • 1
    • 4
    • 5
  • Y. Zhao
    • 2
  1. 1.Department of NeurologySingapore General HospitalSingaporeSingapore
  2. 2.Clinical ResearchSingapore General HospitalSingaporeSingapore
  3. 3.Health ScreeningSingapore General HospitalSingaporeSingapore
  4. 4.National Neuroscience InstituteSingaporeSingapore
  5. 5.SingHealth ResearchSingaporeSingapore
  6. 6.Bankstown Lidcome HospitalUniversity of New South WalesSydneyAustralia
  7. 7.United Christian HospitalHong KongChina
  8. 8.Department of Medicine and TherapeuticsChinese University of Hong KongHong KongChina