系统性红斑狼疮和类风湿关节炎中PARP9启动子甲基化的诊断和临床意义

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI:10.1177/09612033251367586
Atefeh Sohanforooshan Moghaddam, Mitra Salehi, Emran Esmaeilzadeh, Meysam Mosallaei
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引用次数: 0

摘要

目的对系统性红斑狼疮(SLE)和类风湿关节炎(RA)进行准确诊断和持续监测是有效治疗的关键。传统的生物标志物在其敏感性和特异性方面存在局限性。最近的研究强调了DNA甲基化的重要性,特别是在PARP9基因中,与这些疾病有关。本研究检测了SLE和RA患者外周血单个核细胞(PBMCs)中PARP9启动子甲基化,以评估其诊断潜力。方法在本研究中,我们使用甲基化-量化耐内切酶DNA (MethyQESD)方法,评估了75例SLE患者、75例RA患者和同等数量的健康对照的PBMCs中PARP9启动子的定量甲基化水平。结果研究显示,与对照组相比,SLE和RA患者的PARP9启动子甲基化显著降低(p < 0.001)。最佳临界值对于SLE患者为24.31%,敏感性为81.33%,特异性为77.33%;对于RA患者为27.73%,敏感性为77.33%,特异性为70.66%)。ROC曲线分析显示SLE的AUC为0.758,RA的AUC为0.717,反映了中等的诊断准确性(p < 0.001)。此外,PARP9低甲基化与SLE患者抗dsdna水平和RA患者ESR、CRP水平呈负相关,而与SLE组C3、C4水平呈正相关(p < 0.001)。结论parp9启动子低甲基化具有作为SLE和RA诊断标志物的潜力。在SLE和RA患者中,PAPR9启动子的低甲基化与疾病活动性因子之间存在显著关联,这表明PARP9低甲基化可以作为监测疾病活动性的替代生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diagnostic and clinical implications of PARP9 promoter methylation in systemic lupus erythematosus and rheumatoid arthritis.

ObjectiveAccurate diagnosis and continuous monitoring are crucial for effective management of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conventional biomarkers exhibit limitations regarding their sensitivity and specificity. Recent research highlights the importance of DNA methylation, particularly in the PARP9 gene, in relation to these diseases. This study examines PARP9 promoter methylation in peripheral blood mononuclear cells (PBMCs) obtained from SLE and RA patients to evaluate its diagnostic potential.MethodsIn this study, we assessed the quantitative methylation levels of the PARP9 promoter in PBMCs from 75 SLE patients, 75 RA patients, and an equal number of healthy controls using methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.ResultsThe study revealed significant hypomethylation of the PARP9 promoter in both SLE and RA patients compared to control group (p < .001). The optimal cutoff values identified were 24.31% for SLE, demonstrating a sensitivity of 81.33%, and a specificity of 77.33%, and 27.73% for RA patients with a sensitivity of 77.33%, and a specificity of 70.66%). ROC curve analysis showed an AUC of 0.758 for SLE and 0.717 for RA, reflecting a moderate diagnostic accuracy (p < .001). Additionally, hypomethylation of PARP9 was negatively correlated with anti-dsDNA levels in SLE patients and with ESR and CRP levels in RA patients, while showed a positive correlation with C3 and C4 levels in SLE group (p < .001).ConclusionPARP9 promoter hypomethylation shows potential as a diagnostic biomarker for SLE and RA. The significant association between hypomethylation of PAPR9 promoter and disease activity factors in SLE and RA patients, is suggesting that PARP9 hypomethylation could be used as an alternative biomarker for monitoring of disease activity.

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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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