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P89 Epigenome-wide association study reveals differential DNA methylation in systemic lupus erythematosus patients with a history of ischemic heart disease
  1. Juliana Imgenberg-Kreuz1,
  2. Christopher Sjöwall2,
  3. Martina Frodlund2,
  4. Iva Gunnarsson3,
  5. Elisabet Svenungsson3 and
  6. Dag Leonard1
  1. 1Dept. of Medical Sciences, Uppsala University, Uppsala
  2. 2Dept. of Clinical and Experimental Medicine, Linköping University, Linköping
  3. 3Dept. of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden


Background/Purpose Patients with Systemic Lupus Erythematosus (SLE) have an increased risk of ischemic heart disease (IHD). Altered DNA methylation patterns have been reported both in SLE and in individuals with a history of IHD in the general population. We performed a case-case epigenome-wide association study (EWAS) for IHD in patients with SLE to identify phenotype-specific differences in DNA methylation.

Methods DNA methylation profiles from peripheral blood samples of 33 SLE patients with a history of IHD (myocardial infarction and/or angina pectoris) and 66 matched (sex and age) SLE patients without any prior cardiovascular events were generated on the HumanMethylation450k array (Illumina). All patients were female, fulfilled ≥ 4 ACR-82 SLE criteria and were recruited at the Uppsala, Linköping and Karolinska University hospitals, Sweden. A linear regression model including age at sampling, blood cell type distribution and HM450k BeadChip as covariates was fitted, and association p-values were Bonferroni corrected.

Results We identified 210 differentially methylated CpG sites (DMCs) in SLE IHD, with a majority (84%) of sites showing decreased methylation levels in IHD. DMCs were annotated to 155 unique genes, of which 64% were characterized as interferon-induced. DMCs with the largest effect size were located at Complement component 4 binding protein alpha (C4BPA), Membrane spanning 4-domains A3 (MS4A3) and Triggering receptor expressed on myeloid cells 1 (TREM1). Further, a differentially methylated region with multiple DMCs was observed in the promoter region of Programmed cell death 1 gene (PDCD1), where increased methylation was associated with IHD.

Conclusion The results of this study highlight genes and mechanisms that may be implicated in the pathogenesis of and/or recovery from IHD in patients with SLE. Identified DMCs can serve as candidates for functional studies and as potential biomarkers for IHD in patients with SLE.

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