诊断时的DNA甲基化与早期类风湿关节炎中改善病情药物的反应相关。
DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis.
作者信息
Glossop John R, Nixon Nicola B, Emes Richard D, Sim Julius, Packham Jon C, Mattey Derek L, Farrell William E, Fryer Anthony A
机构信息
Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.
Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
出版信息
Epigenomics. 2017 Apr;9(4):419-428. doi: 10.2217/epi-2016-0042. Epub 2016 Nov 25.
AIM
A proof-of-concept study to explore whether DNA methylation at first diagnosis is associated with response to disease-modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA).
PATIENTS & METHODS: DNA methylation was quantified in T-lymphocytes from 46 treatment-naive patients using HumanMethylation450 BeadChips. Treatment response was determined in 6 months using the European League Against Rheumatism (EULAR) response criteria.
RESULTS
Initial filtering identified 21 cytosine-phosphate-guanines (CpGs) that were differentially methylated between responders and nonresponders. After conservative adjustment for multiple testing, six sites remained statistically significant, of which four showed high sensitivity and/or specificity (≥75%) for response to treatment. Moreover, methylation at two sites in combination was the strongest factor associated with response (80.0% sensitivity, 90.9% specificity, AUC 0.85).
CONCLUSION
DNA methylation at diagnosis is associated with disease-modifying antirheumatic drug treatment response in early RA.
目的
一项概念验证性研究，旨在探究初诊时的DNA甲基化是否与早期类风湿关节炎（RA）患者对改善病情抗风湿药物（DMARDs）的反应相关。
患者与方法
使用HumanMethylation450 BeadChips对46例未接受过治疗的患者的T淋巴细胞中的DNA甲基化进行定量分析。采用欧洲抗风湿病联盟（EULAR）反应标准在6个月时确定治疗反应。
结果
初步筛选确定了21个在反应者和无反应者之间存在差异甲基化的胞嘧啶-磷酸-鸟嘌呤（CpG）位点。经过多重检验的保守校正后，6个位点仍具有统计学意义，其中4个位点对治疗反应表现出高敏感性和/或特异性（≥75%）。此外，两个位点的甲基化联合是与反应相关的最强因素（敏感性80.0%，特异性90.9%，曲线下面积0.85）。
结论
初诊时的DNA甲基化与早期RA患者对改善病情抗风湿药物的治疗反应相关。
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