{
  "abstract": "Introduction and Aims Sarcoidosis is a heterogeneous complex disease involving genetic susceptibility and environmental factors. Epigenetic modifications are emerging as important in regulating immune and fibrotic processes through gene expression in lung disease. We aim to assess how differential methylation can provide mechanistic insights into sarcoidosis-specific disease-regulating pathways.Methods 79 patients with sarcoidosis underwent methylation analysis of 100ng of genomic DNA extracted from peripheral white blood cells. Analysis was carried out using the methylkit package in R. Clinical data, including demographics, pulmonary function tests, CXR stage, disease duration and need for treatment were analysed. We stratified patients by the presence or absence of fibrosis on plain CXR at the time of blood draw. Results were cross-referenced to stratification by presence or absence of inflammation (ESR >20, CRP >7). A further targeted approach evaluated involvement of the mTOR pathway.Results The mean age of the cohort was 58.4 (SD 11.6), 66% were male, 54% required treatment, and 41% were fibrotic (n 32). Screening results for > 5 log2 fold or < -5 Log2 fold change identified 9 targets with increased methylation, 29 with decreased methylation, and an additional 20 novel transcripts. Table 1 presents results focusing on methylation of genes found within the CPG island (promoter region), more likely to affect transcription and therefore gene expression. Initial results indicate involvement of Wnt, JN and MAP Kinase pathways. Increased expression of HDAC4 was found in fibrotic patients; these are involved in extracellular matrix production and tissue remodelling processes and may represent a therapeutic target. Targeted evaluation of mTOR revealed significant differential methylation of Forkhead box protein 01 (FOX01), a transcription factor, acting both as a regulator and being regulated by inflammatory pathways, in the inflammatory group (q 0.0126).Abstract P241 Table 1Differential Methylation within CPG Island in Fibrotic Sarcoid PatientsConclusions Methylation profiles may have potential applications as biomarkers for disease identification and prognostication, and personalised treatment strategies. However, our results require validation and further work is required to understand the biological significance of the identified profiles, including their impact on gene expression and cellular processes, as well as clinical outcomes.",
  "authors": [
    {
      "affiliations": [
        "Antrim Area Hospital, Northern HSC Trust, UK"
      ],
      "name": "L Huajian"
    },
    {
      "affiliations": [
        "Antrim Area Hospital, Northern HSC Trust, UK"
      ],
      "name": "P Kenny"
    },
    {
      "affiliations": [
        "C-TRIC, Altnagelvin Hospital, UK"
      ],
      "name": "M Watson"
    },
    {
      "affiliations": [
        "Antrim Area Hospital, Northern HSC Trust, UK"
      ],
      "name": "R Gilpen"
    },
    {
      "affiliations": [
        "Antrim Area Hospital, Northern HSC Trust, UK"
      ],
      "name": "P Logue"
    },
    {
      "affiliations": [
        "Queen’s University Belfast, Belfast, UK"
      ],
      "name": "D Linden"
    },
    {
      "affiliations": [
        "Queen’s University Belfast, Belfast, UK"
      ],
      "name": "P Minnis"
    }
  ],
  "title": "P241 Differential methylation analysis in fibrotic versus non-fibrotic sarcoidosis",
  "uid": "9259e280-a8a4-59e0-8fe6-c63059591c03"
}