DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.

doi:10.1038/s41467-018-04732-5

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Article

DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.

Nature communications - 19 Jun 2018

Kular Lara, Liu Yun, Ruhrmann Sabrina, Zheleznyakova Galina, Marabita Francesco, Gomez-Cabrero David, James Tojo, Ewing Ewoud, Lindén Magdalena, Górnikiewicz Bartosz, Aeinehband Shahin, Stridh Pernilla, Link Jenny, Andlauer Till F M, Gasperi Christiane, Wiendl Heinz, Zipp Frauke, Gold Ralf, Tackenberg Björn, Weber Frank, Hemmer Bernhard, Strauch Konstantin, Heilmann-Heimbach Stefanie, Rawal Rajesh, Schminke Ulf, Schmidt Carsten O, Kacprowski Tim, Franke Andre, Laudes Matthias, Dilthey Alexander T, Celius Elisabeth G, Søndergaard Helle B, Tegnér Jesper, Harbo Hanne F, Oturai Annette B, Olafsson Sigurgeir, Eggertsson Hannes P, Halldorsson Bjarni V, Hjaltason Haukur, Olafsson Elias, Jonsdottir Ingileif, Stefansson Kari, Olsson Tomas, Piehl Fredrik, Ekström Tomas J, Kockum Ingrid, Feinberg Andrew P, Jagodic Maja

Abstract excerpt

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and...

Topics

Adult
Aged
Cells, Cultured
Cohort Studies
DNA Methylation

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Female

Gene Expression Regulation

Genetic Predisposition to Disease

HLA-DRB1 Chains

Humans

Male

Meta-Analysis as Topic

Middle Aged

Multiple Sclerosis

Polymorphism, Single Nucleotide

Risk Factors

Young Adult

Source

Open in PubMed Open full text

Identifiers

PMID: 29921915
DOI: 10.1038/s41467-018-04732-5
PMCID: PMC6008330

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