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

Meeting abstract

Genetic-epigenetic interaction in lupus

AH Sawalha

  • Correspondence: AH Sawalha

Author affiliations

University of Michigan, Ann Arbor, MI, USA

Citation and License

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: http://arthritis-research.com/content/14/S3/A9


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 (http://creativecommons.org/licenses/by/2.0), 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.