Genomics

Dataset Information

54

Joint-specific DNA methylation signatures in rheumatoid arthritis [methylation array]


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 signaling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-seq. 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. Overall design: Fibroblast-like synoviocyte cell-lines from knee and hip joints in rheumatoid arthritis (RA) and osteoarthritis (OA) patients.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip [UBC enhanced annotation v1.0]

SUBMITTER: Gary S Firestein  

PROVIDER: GSE80071 | GEO | 2016-06-09

SECONDARY ACCESSION(S): PRJNA317756

REPOSITORIES: GEO

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Publications

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

Ai Rizi R   Hammaker Deepa D   Boyle David L DL   Morgan Rachel R   Walsh Alice M AM   Fan Shicai S   Firestein Gary S GS   Wang Wei W  

Nature communications 20160610


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. U  ...[more]

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