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This article is part of the supplement: Lupus 2012: New targets, new approaches

Open Badges Meeting abstract

Genetic-epigenetic interaction in lupus

AH Sawalha

  • Correspondence: AH Sawalha

Author Affiliations

University of Michigan, Ann Arbor, MI, USA

Arthritis Research & Therapy 2012, 14(Suppl 3):A9  doi:10.1186/ar3943

The electronic version of this article is the complete one and can be found online at:

Published:27 September 2012

© 2012 Sawalha; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Meeting abstract

Systemic lupus erythematosus is a genetically complex autoimmune disease. A large body of evidence suggests an important role for epigenetic variation, particularly DNA methylation changes, in the pathogenesis of lupus. We recently performed a comprehensive evaluation of the DNA methylome in lupus T cells and identified a number of differentially methylated loci that can contribute to the pathogenesis of the disease. By analyzing the interaction between genetic risk, T-cell DNA demethylation, and the SLEDAI scores, we demonstrated that the (genetic risk)/(T-cell DNA methylation) ratio increased directly with disease activity in lupus patients. Furthermore, men with lupus require a higher genetic risk and/or lower T-cell DNA methylation levels to achieve a lupus flare of equal severity to women, suggesting genetic-epigenetic interaction in explaining the sex bias in lupus. We have also established the genetic region containing methyl-CpG-binding protein 2 (MECP2) as a lupus susceptibility locus. MeCp-2 is a key transcription factor critically involved in regulating the expression of methylation-sensitive genes, and directly recruits DNA methyltransferase 1 (DNMT1). Indeed, recent data from our group demonstrate that the lupus-associated variants in MECP2 induce DNA methylation changes in key inflammatory genes. Our data suggest that efforts to study genetic-epigenetic interactions in lupus will further our understanding of the disease pathogenesis and might help to explain, at least in part, the missing heritability in lupus.