Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1
- 12 January 2012
- journal article
- research article
- Published by Springer Nature in neurogenetics
- Vol. 13 (1) , 87-91
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.Keywords
This publication has 17 references indexed in Scilit:
- Epigenetic and genetic silencing of CHFR in esophageal adenocarcinomasCancer, 2010
- Conserved role of intragenic DNA methylation in regulating alternative promotersNature, 2010
- Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson's Disease Patients' BrainsJournal of Neuroscience, 2010
- Defensins as Anti-Inflammatory Compounds and Mucosal AdjuvantsFuture Microbiology, 2009
- MPTP-induced model of Parkinson's disease in cytochrome P450 2E1knockout miceNeuropharmacology, 2009
- Failure of neuronal homeostasis results in common neuropsychiatric phenotypesNature, 2008
- Cytochrome P450 2E1 in the substantia nigra: Relevance for dopaminergic neurotransmission and free radical productionSynapse, 2008
- DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated NeuronsPLOS ONE, 2007
- Phenotypic plasticity and the epigenetics of human diseaseNature, 2007
- Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholicsBritish Journal of Pharmacology, 2003