Skewed X-chromosome inactivation and XIST locus methylation levels does not contribute to the lower prevalence of Parkinson´s disease in females

Publication date: Available online 6 June 2017
Source:Neurobiology of Aging
Author(s): Amit Sharma, Oliver Kaut, Anna Pavlova, Holger Fröhlich, Ashar Ahmad, Ina Schmitt, Osman El-Maarri, Johannes Oldenburg, Ullrich Wüllner
Parkinson's disease (PD) is a degenerative disorder of the nervous system and the cause of the majority of sporadic cases is unknown. Females are relatively protected from PD as compared to males and linkage studies suggested a PD susceptibility locus on the X chromosome. To determine a putative association of skewed X-chromosome inactivation (XCI) and PD, we examined XCI patterns using a human androgen receptor gene-based assay (HUMARA) and did not identify any association of skewed or random X inactivation with clinical heterogeneity among female patients. In addition, we sought to determine methylation specific changes at the XIST (X-inactive specific transcript) locus, which is known to be responsible for initiating X-inactivation and observed a trend towards hypomethylation in the gene body region of the XIST locus in PD females. Furthermore, we extend our analysis for DNA methylation across the entire X-chromosome and revealed no methylation specific differences between PD females and healthy controls. Herein, we propose that unlike hormones, skewed XCI might not have any protective role against PD in females.



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