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A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity

Genes & Immunity volume 13, pages 214–220 (2012)Cite this article

Abstract

The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

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Acknowledgements

We would like to thank all of the SLE patients and healthy controls who participated in this study, as well as I-Ting Chung (GeneTech Biotech, Taipei, Taiwan) for helping with the array analysis. This work was supported by grants from the National Scientific Council (NSC 99-2314-B-002 -072 -MY3 and NSC 98-2314-B-002-142), from the National Taiwan University Hospital-Taipei Veterans General Hospital joint research program (NTUH-TVGH100-07) and from National Taiwan University Hospital (NTUH.100-M1747).

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Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    S-Y Lin

  2. Department of Obstetrics and Gynecology, Hsin Chu Branch National Taiwan University Hospital, Taipei, Taiwan

    S-Y Lin

  3. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    S-C Hsieh

  4. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

    Y-C Lin, M-H Tsai, L-C Lai & E Y Chuang

  5. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan

    C-N Lee, Y-N Su & H-N Ho

  6. Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan

    P-C Chen & Y-N Su

  7. Graduate Institute of Clinical Genomics, National Taiwan University, Taipei, Taiwan

    C-C Hung & L-Y Chen

  8. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    W S Hsieh

  9. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan

    D-M Niu

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  1. S-Y Lin
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Correspondence to Y-N Su.

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Lin, SY., Hsieh, SC., Lin, YC. et al. A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity. Genes Immun 13, 214–220 (2012). https://doi.org/10.1038/gene.2011.74

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