Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients

Abstract The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This...

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Autores principales:	Vicki E. Maltby, Rodney A. Lea, Sean Burnard, Alexandre Xavier, Thao Van Cao, Nicole White, Daniel Kennedy, Kira Groen, Katherine A. Sanders, Rebecca Seeto, Samara Bray, Melissa Gresle, Louise Laverick, Helmut Butzkueven, Rodney J. Scott, Jeannette Lechner-Scott
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d27ddf73fb74666a6a7c7b44026b9c1
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spelling	oai:doaj.org-article:8d27ddf73fb74666a6a7c7b44026b9c12021-12-02T13:58:10ZEpigenetic differences at the HTR2A locus in progressive multiple sclerosis patients10.1038/s41598-020-78809-x2045-2322https://doaj.org/article/8d27ddf73fb74666a6a7c7b44026b9c12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78809-xhttps://doaj.org/toc/2045-2322Abstract The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4+ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.Vicki E. MaltbyRodney A. LeaSean BurnardAlexandre XavierThao Van CaoNicole WhiteDaniel KennedyKira GroenKatherine A. SandersRebecca SeetoSamara BrayMelissa GresleLouise LaverickHelmut ButzkuevenRodney J. ScottJeannette Lechner-ScottNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vicki E. Maltby Rodney A. Lea Sean Burnard Alexandre Xavier Thao Van Cao Nicole White Daniel Kennedy Kira Groen Katherine A. Sanders Rebecca Seeto Samara Bray Melissa Gresle Louise Laverick Helmut Butzkueven Rodney J. Scott Jeannette Lechner-Scott Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
description	Abstract The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4+ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.
format	article
author	Vicki E. Maltby Rodney A. Lea Sean Burnard Alexandre Xavier Thao Van Cao Nicole White Daniel Kennedy Kira Groen Katherine A. Sanders Rebecca Seeto Samara Bray Melissa Gresle Louise Laverick Helmut Butzkueven Rodney J. Scott Jeannette Lechner-Scott
author_facet	Vicki E. Maltby Rodney A. Lea Sean Burnard Alexandre Xavier Thao Van Cao Nicole White Daniel Kennedy Kira Groen Katherine A. Sanders Rebecca Seeto Samara Bray Melissa Gresle Louise Laverick Helmut Butzkueven Rodney J. Scott Jeannette Lechner-Scott
author_sort	Vicki E. Maltby
title	Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
title_short	Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
title_full	Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
title_fullStr	Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
title_full_unstemmed	Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
title_sort	epigenetic differences at the htr2a locus in progressive multiple sclerosis patients
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8d27ddf73fb74666a6a7c7b44026b9c1
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Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients

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