Distinctive patterns of DNA methylation associated with Parkinson disease

Abstract

Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved in etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification of early pathological changes is crucial to enable therapeutic interventions before major neuropathological damage occurs. Here we investigated genome-wide DNA methylation in brain and blood samples from PD patients and observed a distinctive pattern of methylation involving many genes previously associated to PD, therefore supporting the role of epigenetic alterations as a molecular mechanism in neurodegeneration. Importantly, we identified concordant methylation alterations in brain and blood, suggesting that blood might hold promise as a surrogate for brain tissue to detect DNA methylation in PD and as a source for biomarker discovery.

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

“…Concordant DNA methylation profiles in brain and blood samples from the same individuals suggest that blood might hold promise as surrogate for brain tissue to detect DNA methylation. [28][29][30] Genome-wide methylation arrays revealed similar methylation patterns for the HOX genes in breast cancers and white blood cells, which suggests that methylation is more likely to be a normal developmental and tissue-specific process that does not directly relate to the malignant mechanism. 31 Interestingly, functional in silico analysis using the MENT database showed no correlation with gene expression in normal brain and blood tissues for the methylation of 2 HOXB7 promoter CpGs but there is evidence that lower HOXB7 methylation values in brain tightly regulate Figure 3.…”

Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review

“…As exemplified in several reviews but particularly in the current one, epigenetic research has been conducted on a number of tissues including postmortem brain samples together with peripheral tissues such as saliva and blood. Epigenetic signatures are known to differ from one tissue to another; nevertheless, recent studies encourage the common assumption of epigenetic hallmarks in blood being replicable in brain tissues (Ewald et al, 2014;Masliah et al, 2013).…”

Comorbidities in Neurology: Is adenosine the common link?

“…DNA methylation profiles of human hippocampus from AD patients, revealed promoter hypermethylation of the dual-specificity phosphatase 22 (DUSP22) gene, which is a likely candidate gene for the pathogenesis of AD since it determines tau phosphorylation status and CREB signaling (Sanchez-Mut et al, 2014). Distinct changes in DNA methylation patterns have also been observed in patients with PD and ALS (Martin and Wong, 2013; Masliah et al, 2013) and increased global DNA methylation has been suggested as a biomarker for ALS (Tremolizzo et al, 2014). Together, these findings suggest that epilepsy and neurodegenerative conditions may share global changes in the methylome as a consequence of altered adenosine homeostasis.…”