Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes

被引:51
作者
Glossop, John R. [1 ,2 ]
Emes, Richard D. [3 ,4 ]
Nixon, Nicola B. [2 ]
Packham, Jon C. [2 ]
Fryer, Anthony A. [1 ]
Mattey, Derek L. [1 ,2 ]
Farrell, William E. [1 ]
机构
[1] Keele Univ, Guy Hilton Res Ctr, Inst Sci & Technol Med, Thornburrow Dr, Stoke On Trent ST4 7QB, Staffs, England
[2] Haywood Hosp, Haywood Rheumatol Ctr, High Lane, Stoke On Trent ST6 7AG, Staffs, England
[3] Univ Nottingham, Sch Vet Med & Sci, Sutton Bonington Campus, Loughborough LE12 5RD, Leics, England
[4] Univ Nottingham, Adv Data Anal Ctr, Sutton Bonington Campus, Loughborough LE12 5RD, Leics, England
关键词
B lymphocyte; CpG; DNA methylation; early rheumatoid arthritis; genome-wide; Illumina 450K array; T lymphocyte; treatment naive; SINGLE CPG SITE; METHYLATION PATTERNS; UPSTREAM ENHANCER; CELL-FUNCTION; FOXP3; HYPOMETHYLATION; IDENTIFICATION; DEMETHYLATION; METHOTREXATE; DISCOVERY;
D O I
10.2217/epi.15.103
中图分类号
Q3 [遗传学];
学科分类号
071007 [遗传学];
摘要
Aim: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. Patients & methods: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals. Results: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. Conclusion: Treatment-naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA.
引用
收藏
页码:209 / 224
页数:16
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