Distúrbios cerebrais e terapia

Abstrato

DNA Methylation of Imprinted Loci on Autosomal Chromosomes and IGF2 are not Affected in Parkinson's Disease Patients Peripheral Blood Monocytes

Oliver Kaut, Amit Sharma, Ullrich Wüllner

Genomic imprinting is an epigenetic phenomenon that results in differential expression of alleles depending on their parental origin. The functional significance of DNA methylation in genomic imprinting has been widely investigated and to date, around 100 imprinted genes have been identified in humans. To investigate, if methylation status of these “known” imprinting genes is associated with Parkinson's disease (PD), we analyzed methylation profile of all these “known” imprinting genes using an epigenome wide approach with Illumina's 450K methylation chip. Strikingly, none of these total autosomal annotated genes show changes of DNA methylation between PD and healthy individuals. We further refined our analysis by evaluating DNA methylation for maternally imprinted human gene encoding insulin-like growth factor 2 (IGF2) by using bisulfite sequencing PCR (BSP) and by considering different dosages of L-dopa. Our results demonstrate that methylation profiles specifically at exon 8-9 genomic region of IGF2 gene in PD are neither influenced by the dosage of L-dopa treatment nor by the disease itself. Thus loss or disruption of imprinting in autosomal chromosomes seems not to apparent in PD and is not relevant for the pathogenesis of the disease.