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This study aimed to investigate whether methylation changes at BPA-sensitive 5\u2019-C-phosphate-G-3\u2019 (CpG) sites are associated with SLE and clinical subphenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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 \u22652 of 7 BPA exposure studies and supported by cell line data. A BPA\n                      <jats:sub>All<\/jats:sub>\n                      score including 19 CpGs and a BPA\n                      <jats:sub>SLE<\/jats:sub>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with SLE had significantly higher BPA\n                      <jats:sub>SLE<\/jats:sub>\n                      score than controls in the discovery (OR 1.34, p=4.6\u00d710\n                      <jats:sup>-13<\/jats:sup>\n                      ), replication (OR 1.28, p=1.1\u00d710\n                      <jats:sup>-5<\/jats:sup>\n                      ) and meta-analysis (OR 1.32, p=3.3\u00d710\n                      <jats:sup>-17<\/jats:sup>\n                      ). Higher BPA\n                      <jats:sub>All<\/jats:sub>\n                      score was associated with SLE in the discovery cohort (OR 1.05, p=2.3\u00d710\n                      <jats:sup>-3<\/jats:sup>\n                      ) 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\u00d710\n                      <jats:sup>-4<\/jats:sup>\n                      ). Both scores were associated with prednisolone treatment (p&lt;0.001), and the BPA\n                      <jats:sub>SLE<\/jats:sub>\n                      score was associated with serositis and autoantibodies (p&lt;0.05). Transcriptomic analysis of BPA-treated cells revealed enrichment in pathways such as interferon and mitogen-activated protein kinase signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006021","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:25:31Z","timestamp":1758792331000},"page":"e006021","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Patients with systemic lupus erythematosus (SLE) have an increased bisphenol A methylation score linked to SLE risk genes and selected clinical 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