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

Neurogenetics. 2012 Feb;13(1):87-91. doi: 10.1007/s10048-011-0308-3. Epub 2012 Jan 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cerebral Cortex / physiology
  • Cluster Analysis
  • Cytochrome P-450 CYP2E1 / genetics*
  • Cytochrome P-450 CYP2E1 / metabolism*
  • DNA Methylation*
  • Female
  • Genome, Human*
  • Humans
  • Male
  • Parkinson Disease / enzymology*
  • Parkinson Disease / genetics*
  • Putamen / physiology
  • RNA, Messenger / metabolism*

Substances

  • RNA, Messenger
  • Cytochrome P-450 CYP2E1