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The expression of zinc finger 804a (ZNF804a) and cyclin-dependent kinase 1 (CDK1) genes is related to the pathogenesis of rheumatoid arthritis.

锌指 804a (ZNF804a) 和细胞周期蛋白依赖性激酶 1 (CDK1) 基因的表达与类风湿关节炎的发病有关。

  • 影响因子:1.64
  • DOI:10.1080/13813455.2020.1716810
  • 作者列表:"Fattah SA","Abdel Fattah MA","Mesbah NM","Saleh SM","Abo-Elmatty DM","Mehanna ET
  • 发表时间:2020-01-29
Abstract

ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

摘要

ZNF804a 和 CDK1 基因编码参与炎症通路的蛋白。本研究旨在研究 RA 中 ZNF804a 和 CDK1 表达谱与疾病活动性和严重程度的相关性,并评估其与埃及 RA 患者炎症反应的相关性。使用定量 PCR (qRT-PCR) 评估 ZNF804a 和 CDK1 表达谱。评估临床和实验室参数。与健康对照组相比,RA 患者 ZNF804a 表达下调 0.177 倍,而 CDK1 表达上调至 3.29 倍 (  <.001)。ZNF804a 下调与 CRP 、 RF 、 28 关节疾病活动评分 (DAS) 使用 CRP (DAS-CRP) 和 TNF-α 呈负相关。RA 患者 CDK1 过表达与 IFN-1 、 ACPA 相关。ZNF804a 和 CDK1 基因与 RA 发病有关,它们对 TNF-α 和 IFN-1 的影响有助于 RA 患者的炎症反应。

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影响因子:2.42
发表时间:2020-01-29
来源期刊:Autoimmunity
DOI:10.1080/08916934.2019.1710831
作者列表:["Gomes da Silva IIF","Lima CAD","Monteiro MLA","Barboza DASP","Rushansky E","Mariano MHQA","Sandrin-Garcia P","de Souza PRE","Maia MMD"]

METHODS:Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in and genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92;  = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index ( = .021) and rs2430561 with DAS28 ( = .029) and CDAI ( = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index  < .001) and ESR ( = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ ( = 5.497;  < .001) and ESR ( = 2.727;  = .032)). Our analysis indicated that in the studied population +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.

翻译标题与摘要 下载文献
影响因子:1.64
发表时间:2020-01-29
DOI:10.1080/13813455.2020.1716810
作者列表:["Fattah SA","Abdel Fattah MA","Mesbah NM","Saleh SM","Abo-Elmatty DM","Mehanna ET"]

METHODS:ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

翻译标题与摘要 下载文献
影响因子:9.18
发表时间:2020-01-29
DOI:10.1136/annrheumdis-2019-216539
作者列表:["Emery P","Horton S","Dumitru RB","Naraghi K","van der Heijde D","Wakefield RJ","Hensor EMA","Buch MH"]

METHODS:OBJECTIVES:We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS:Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS:We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS:Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested.Trial registration numberNCT02433184.

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