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白细胞线粒体 DNA 拷贝数是一种潜在的非侵入性银屑病生物标志物。

Leukocyte mitochondrial DNA copy number is a potential non-invasive biomarker for psoriasis.

机构信息

Faculty of Allied Health, Department of Medical Laboratory, Kuwait University, State of Kuwait.

Department of Molecular Medicine and Al-Jawhara Centre for Molecular Medicine, Genetics, and Inherited Disorders, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.

出版信息

PLoS One. 2022 Jun 29;17(6):e0270714. doi: 10.1371/journal.pone.0270714. eCollection 2022.

Abstract

Abnormalities in the mitochondria have been linked to psoriasis, a chronic immune-mediated inflammatory skin disease. The mitochondrial DNA (mtDNA) is present in thousands of copies per cell and altered mtDNA copy number (mtDNA-CN), a common indicator of mitochondrial function, has been proposed as a biomarker for several diseases including autoimmune diseases. In this case-control study, we investigated whether the mtDNA-CN is related to psoriasis, correlates with the disease duration and severity, and can serve as a disease biomarker. Relative mtDNA-CN as compared with nuclear DNA was measured by a quantitative real-time polymerase chain reaction in peripheral blood buffy coat samples from 56 patients with psoriasis and 44 healthy controls. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of mtDNA-CN as a biomarker. We found that the mtDNA-CN was significantly decreased in patients with psoriasis compared to healthy controls (93.6±5.3 vs. 205±71; P = 0.04). Sub-group analyses with stratification of patients based on disease duration under or over 10 years and disease severity indicated that the mtDNA-CN was significantly lower in patients with longer disease duration (74±4.3 in disease duration >10 years vs. 79±8.3 in disease duration <10 years, P = 0.009), and higher disease severity (72±4.3 in moderate-to-severe index vs. 88.3 ± 6 in mild index, P = 0.017). Moreover, the mtDNA-CN was negatively correlated with the disease duration and disease severity (r = -0.36, P = 0.006; r = -0.41, P = 0.003 respectively). The ROC analysis of mtDNA-CN showed an area under the curve (AUC) of 0.84 (95% confidence interval: 0.69-0.98; P = 0.002) for differentiating patients from healthy controls. Our study suggests that low mtDNA-CN may be an early abnormality in psoriasis and associates with the disease progression. Our study also suggests that mtDNA-CN may be a novel blood-based biomarker for the early detection of psoriasis.

摘要

线粒体异常与银屑病有关,银屑病是一种慢性免疫介导的炎症性皮肤病。线粒体 DNA(mtDNA)在每个细胞中存在数千个拷贝,改变的 mtDNA 拷贝数(mtDNA-CN),一种常见的线粒体功能指标,已被提出作为几种疾病的生物标志物,包括自身免疫性疾病。在这项病例对照研究中,我们研究了 mtDNA-CN 是否与银屑病有关,是否与疾病的持续时间和严重程度相关,以及是否可以作为疾病的生物标志物。通过定量实时聚合酶链反应测量外周血白细胞层样本中的相对 mtDNA-CN 与核 DNA,比较 56 例银屑病患者和 44 例健康对照者。通过接受者操作特征(ROC)曲线分析评估 mtDNA-CN 作为生物标志物的价值。我们发现,与健康对照组相比,银屑病患者的 mtDNA-CN 显著降低(93.6±5.3 与 205±71;P=0.04)。根据疾病持续时间 10 年以上或以下以及疾病严重程度进行分层的亚组分析表明,mtDNA-CN 在疾病持续时间较长的患者中显著降低(疾病持续时间>10 年的患者为 74±4.3,疾病持续时间<10 年的患者为 79±8.3,P=0.009),疾病严重程度较高的患者(中重度指数的患者为 72±4.3,轻度指数的患者为 88.3±6,P=0.017)。此外,mtDNA-CN 与疾病持续时间和疾病严重程度呈负相关(r=-0.36,P=0.006;r=-0.41,P=0.003)。mtDNA-CN 的 ROC 分析显示,区分患者与健康对照组的曲线下面积(AUC)为 0.84(95%置信区间:0.69-0.98;P=0.002)。我们的研究表明,低 mtDNA-CN 可能是银屑病的早期异常,并与疾病进展有关。我们的研究还表明,mtDNA-CN 可能是一种新型基于血液的银屑病早期检测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbf/9242485/9a9c42a7b7d1/pone.0270714.g001.jpg

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