Skip to main content

Genetic-epigenetic interaction in lupus

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to AH Sawalha.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Sawalha, A. Genetic-epigenetic interaction in lupus. Arthritis Res Ther 14, A9 (2012). https://doi.org/10.1186/ar3943

Download citation

Keywords

  • Systemic Lupus Erythematosus
  • SLEDAI Score
  • High Genetic Risk
  • Lupus Flare
  • Complex Autoimmune Disease