{
  "abstract": "Objectives Bisphenol A (BPA), a xenoestrogen that can alter DNA methylation status, has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study aimed to investigate whether methylation changes at BPA-sensitive 5’-C-phosphate-G-3’ (CpG) sites are associated with SLE and clinical subphenotypes.Methods A discovery cohort (n=747) and a replication cohort (n=388) including Swedish patients with SLE and healthy controls were investigated using the Illumina HM450k bead chip. BPA-sensitive CpG sites were selected if differentially methylated in ≥2 of 7 BPA exposure studies and supported by cell line data. A BPA All score including 19 CpGs and a BPASLE score based on three CpG sites co-localised in the genome with SLE risk loci were calculated for each individual, analysed for associations with clinical data and then compared with publicly available transcriptomic data from BPA-treated cells.Results Patients with SLE had significantly higher BPA SLE score than controls in the discovery (OR 1.34, p=4.6×10-13), replication (OR 1.28, p=1.1×10-5) and meta-analysis (OR 1.32, p=3.3×10-17). Higher BPAAll score was associated with SLE in the discovery cohort (OR 1.05, p=2.3×10-3) but not in the replication cohort (OR 1.04, p=0.12) with a significant difference in the meta-analysis (OR 1.05, p=7.0×10-4). Both scores were associated with prednisolone treatment (p<0.001), and the BPASLE score was associated with serositis and autoantibodies (p<0.05). Transcriptomic analysis of BPA-treated cells revealed enrichment in pathways such as interferon and mitogen-activated protein kinase signalling.Conclusions Our findings reveal a novel association between BPA exposure and DNA methylation changes in SLE, with potential implications for the regulation of immune-related gene expression.",
  "authors": [
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Holme Vestin"
    },
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Nina Oparina"
    },
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Maija-Leena Eloranta"
    },
    {
      "affiliations": [
        "Linkoping University Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Martina Frodlund"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Linkoping University Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Christopher Sjöwall"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Lars Rönnblom"
    },
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Juliana Imgenberg-Kreuz"
    },
    {
      "affiliations": [
        "Uppsala University Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    }
  ],
  "title": "Patients with systemic lupus erythematosus (SLE) have an increased bisphenol A methylation score linked to SLE risk genes and selected clinical subphenotypes",
  "uid": "c088d28a-c2ca-511e-bb3c-7c8e6d034625"
}