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

Abstract：

: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 with 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 PD patients. In addition, we sought to determine methylation-specific changes at the X-inactive specific transcript (XIST) locus, which is known to be responsible for initiating X inactivation. We observed a trend towards hypomethylation in the gene body region of the XIST locus in PD females which did not reach significance. Furthermore, we extended our analysis of DNA methylation across the entire X-chromosome which revealed no methylation-specific differences between PD females and healthy controls. Thus, we propose that skewed XCI and methylation levels on the entire X chromosome did not reveal changes which could account for the decreased PD susceptibility in females or suitable to use as a biomarker.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Sharma A,Kaut O,Pavlova A,Fröhlich H,Ahmad A,Schmitt I,El-Maarri O,Oldenburg J,Wüllner U

doi

10.1016/j.neurobiolaging.2017.05.021

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

248.e1-248.e5

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(17)30188-4

journal_volume

57

pub_type

杂志文章

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