Alterations in DNA Methylation Status Associated with Gulf War Illness.

Abstract:

:Gulf War Illness (GWI) affects about 25% of Persian Gulf veterans with a cluster of chronic symptoms, including immune dysfunction and neurological issues. Recent studies implicate gene expression changes in immune function to be associated with GWI. Since DNA methylation can regulate such changes in gene expression, and disruption of DNA methylation pattern is implicated in various immune and neurological diseases, we aimed to study the DNA methylation patterns in peripheral blood mononuclear cells from GWI patients. Global DNA methylation levels were similar in GWI patients and controls. However, the genome-wide microarray technology detected 10,767 differentially methylated CpG sites across gene regulatory elements and within coding regions. Approximately 88% of them were hypermethylated in GWI patients. The separate analysis found 776 differentially methylated gene promoters (DMP), which were predominantly hypermethylated. Pyrosequencing validation confirmed microarray results. Functional analysis revealed that majority of the DMPs belonged to genes responsible for metabolism and immune system. This is the first pilot human study characterizing genome-wide epigenetic changes associated with GWI. It suggests a significant contribution of epigenetic dysfunction in GWI. Moreover, it supports the dysregulation of immune function in GWI. Lastly, it suggests studies with the larger cohort to validate our findings.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Trivedi MS,Abreu MM,Sarria L,Rose N,Ahmed N,Beljanski V,Fletcher MA,Klimas NG,Nathanson L

doi

10.1089/dna.2018.4469

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

561-571

issue

6

eissn

1044-5498

issn

1557-7430

journal_volume

38

pub_type

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