title: A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity.
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.
authors: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: S-Y
authors: SY
authors: Lin
authors: S-C
authors: SC
authors: Hsieh
authors: Y-C
authors: YC
authors: Lin
authors: C-N
authors: CN
authors: Lee
authors: M-H
authors: MH
authors: Tsai
authors: L-C
authors: LC
authors: Lai
authors: E Y
authors: EY
authors: Chuang
authors: P-C
authors: PC
authors: Chen
authors: C-C
authors: CC
authors: Hung
authors: L-Y
authors: LY
authors: Chen
authors: W S
authors: WS
authors: Hsieh
authors: D-M
authors: DM
authors: Niu
authors: Y-N
authors: YN
authors: Su
authors: H-N
authors: HN
authors: Ho
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics* / Q000276:immunology
chemical_list: D053574:Receptors, Interleukin-1 Type II; D016753:Interleukin-10