Ethnicity-specific epigenetic variation in naïve CD4+ T cells and the susceptibility to autoimmunity. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Coit, Patrick; Ognenovski, Mikhail; Gensterblum, Elizabeth; Maksimowicz-McKinnon, Kathleen; Wren, Jonathan; Sawalha, Amr
• Is Part Of: Epigenetics & chromatin. Volume 8:Issue 1(2015)
• Page Start: 1
• Page End: 13
• Publication Date: 2015-12
• Subjects: Epigenetic -- Autoimmunity -- Lupus -- Ethnicity specific -- Genetic -- T cell; Epigenesis -- Periodicals; Chromatin -- Periodicals; 572.8
• DOI: 10.1186/s13072-015-0037-1
• Languages: English
• ISSNs: 1756-8935

Abstract

Abstract Background Genetic 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. Results Impressive 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 asIL32, CD226, CDKN1A, andPTPRN2 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 theIL32 promoter region reduces gene expression in vitro. Importantly, bisulfite DNA sequencing demonstrated thatcis -acting genetic variants within and directly disrupting CpG sites account for some ethnicity-specific variability in DNA methylation. Conclusion Ethnicity-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.