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Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes

Author

Listed:
  • Rizi Ai

    (University of California San Diego)

  • Deepa Hammaker

    (School of Medicine, University of California San Diego)

  • David L. Boyle

    (School of Medicine, University of California San Diego)

  • Rachel Morgan

    (School of Medicine, University of California San Diego)

  • Alice M. Walsh

    (Janssen Research and Development)

  • Shicai Fan

    (University of California San Diego
    School of Automation Engineering, University of Electronic Science and Technology of China)

  • Gary S. Firestein

    (School of Medicine, University of California San Diego)

  • Wei Wang

    (University of California San Diego)

Abstract

Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients.

Suggested Citation

  • Rizi Ai & Deepa Hammaker & David L. Boyle & Rachel Morgan & Alice M. Walsh & Shicai Fan & Gary S. Firestein & Wei Wang, 2016. "Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11849
    DOI: 10.1038/ncomms11849
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