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Epigenetics and Chromatin

, 8:49

First Online: 24 November 2015Received: 03 October 2015Accepted: 14 October 2015

Abstract

BackgroundGenetic and epigenetic variability contributes to the susceptibility and pathogenesis of autoimmune diseases. T cells play an important role in several autoimmune conditions, including lupus, which is more common and more severe in people of African descent. To investigate inherent epigenetic differences in T cells between ethnicities, we characterized genome-wide DNA methylation patterns in naïve CD4+ T cells in healthy African-Americans and European-Americans, and then confirmed our findings in lupus patients.

ResultsImpressive ethnicity-specific clustering of DNA methylation profiling in naïve CD4+ T cells was revealed. Hypomethylated loci in healthy African-Americans were significantly enriched in pro-apoptotic and pro-inflammatory genes. We also found hypomethylated genes in African-Americans to be disproportionately related to autoimmune diseases including lupus. We then confirmed that these genes, such as IL32, CD226, CDKN1A, and PTPRN2 were similarly hypomethylated in lupus patients of African-American compared to European-American descent. Using patch DNA methylation and luciferase reporter constructs, we showed that methylation of the IL32 promoter region reduces gene expression in vitro. Importantly, bisulfite DNA sequencing demonstrated that cis-acting genetic variants within and directly disrupting CpG sites account for some ethnicity-specific variability in DNA methylation.

ConclusionEthnicity-specific inherited epigenetic susceptibility loci in CD4+ T cells provide clues to explain differences in the susceptibility to autoimmunity and possibly other T cell-related diseases between populations.

KeywordsEpigenetic Autoimmunity Lupus Ethnicity specific Genetic T cell AbbreviationsSLESystemic lupus erythematosus

CpGCytosine–phosphate–guanosine

DAVIDDatabase of Annotation, Visualization and Integrated Discovery

GOGene ontology

LINE-1Long interspersed nucleotide element 1

AAAfrican-American

EAEuropean-American

YRIYoruba from Ibadan

CEUCEPH Centre d’Etude du Polymorphisme Humain from Utah

NgNeurogranin

FDRFalse discovery rate

Electronic supplementary materialThe online version of this article doi:10.1186-s13072-015-0037-1 contains supplementary material, which is available to authorized users.

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Autor: Patrick Coit - Mikhail Ognenovski - Elizabeth Gensterblum - Kathleen Maksimowicz-McKinnon - Jonathan D. Wren - Amr H. Sawa

Fuente: https://link.springer.com/



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