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Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1

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Abstract

Multiple lines of evidence suggest a link between environmental toxins and Parkinson's disease (PD). Although numerous studies reported associations of genetic variants in de-toxifying enzymes, i.e. cytochrome genes, with PD. Epigenetic modifications of genes and subsequent altered expression may confer a yet unappreciated level of susceptibility. We present a genome-wide methylation analysis of PD with quantitative DNA methylation levels of 27.500 CpG sites representing 14.495 genes. We found decreased methylation of the cytochrome P450 2E1 gene and increased expression of CYP2E1 messenger RNA in PD patients' brains, suggesting that epigenetic variants of this cytochrome contribute to PD susceptibility.

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Acknowledgements

This study was supported by GlaxoSmithKline (GSK research grant to OK) and in part by the intramural Bonfor research program of the University of Bonn (UW), the Deutsche Parkinson Vereinigung (dPV, Hans-Tauber-Stiftung) and the German Research council (DFG: WU 184/9-1). We gratefully acknowledge, the German Brain Bank (Munich) and Peter Riederer at University of Würzburg for providing tissue samples, and Dr. A. Waha for helpful discussions. The excellent technical work of Anne Hanke, Hassan Khazneh and Sabine Proske-Schmitz is gratefully acknowledged.

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Authors and Affiliations

  1. University Clinic, Department of Neurology, University of Bonn, Bonn, Germany

    Oliver Kaut & Ullrich Wüllner

  2. University Clinic, Department of Neurology, DZNE, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany

    Ina Schmitt

Authors
  1. Oliver Kaut
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  2. Ina Schmitt
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  3. Ullrich Wüllner
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Corresponding authors

Correspondence to Oliver Kaut or Ullrich Wüllner.

Electronic supplementary material

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Clinical data of the individuals included in this study (PDF 144 kb)

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Hypermethylated genes in putamen (PDF 7 kb)

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Kaut, O., Schmitt, I. & Wüllner, U. Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1. Neurogenetics 13, 87–91 (2012). https://doi.org/10.1007/s10048-011-0308-3

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  • DOI: https://doi.org/10.1007/s10048-011-0308-3

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