Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Health Management, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
PLoS One. 2022 May 26;17(5):e0261390. doi: 10.1371/journal.pone.0261390. eCollection 2022.
Brugada syndrome (BrS) can be diagnosed by a type 1 BrS tracing in a 12-lead electrocardiogram (ECG). However, there are daily variations in the ECGs of BrS patients, which presents a challenge when diagnosing BrS. Although many susceptibility genes have been identified, the SCN5A gene is reportedly the main causative gene of BrS. However, most patients do not have an evidence of genetic predisposition to develop BrS. In addition, the diagnosis and risk stratification for ventricular fibrillation (VF) in patients with BrS presents some problems. Meanwhile, circulating micro RNAs (miRNAs) have drawn increased attention as potential biomarkers of various diseases. We hypothesize that circulating miRNAs may be potential diagnostic biomarkers for BrS.
We enrolled 70 Japanese BrS patients and 34 controls for the screening cohort. A total of 2,555 miRNA sequences were detected using the 3D-Gene miRNAs labeling kit and 3D-Gene Human miRNAs Oligo Chip. We compared the expression of the miRNAs between the BrS patients and the controls. We validated whether the miRNA were significantly up- or downregulated in the screening cohort using RT-PCR. We also enrolled 72 Japanese BrS patients and 56 controls to replicate these miRNAs.
Eight miRNAs (hsa-miR-223-3p, hsa-miR-22-3p, hsa-miR-221-3p, hsa-miR-4485-5p, hsa-miR-550a-5p, hsa-miR-423-3p, hsa-miR-23a-3p, and hsa-miR-30d-5p) were downregulated, and one miRNA (hsa-miR-873-3p) was upregulated by more than 3-fold in BrS patients. The multivariate logistic regression analysis determined that hsa-miR-423-3p, hsa-miR-223-3p, and hsa-miR-23a-3p were independently associated with BrS (P < 0.0001). The AUC based on cross validation was 0.871 with a sensitivity and specificity of 83.5% and 81.1%, respectively.
The plasma miRNAs are potential noninvasive biomarkers of BrS, and the constructed logistic model was useful for discriminating BrS.
Brugada 综合征（BrS）可通过 12 导联心电图（ECG）中的 1 型 BrS 描记来诊断。然而，BrS 患者的 ECG 存在日常变化，这给 BrS 的诊断带来了挑战。尽管已经发现了许多易感基因，但 SCN5A 基因据报道是 BrS 的主要致病基因。然而，大多数患者没有遗传易感性的证据来发展 BrS。此外，BrS 患者的室性心动过速（VF）的诊断和风险分层也存在一些问题。同时，循环 microRNAs（miRNAs）作为各种疾病潜在的生物标志物引起了越来越多的关注。我们假设循环 miRNAs 可能是 BrS 的潜在诊断生物标志物。
我们纳入了 70 名日本 BrS 患者和 34 名对照作为筛查队列。使用 3D-Gene miRNAs 标记试剂盒和 3D-Gene Human miRNAs Oligo Chip 检测了 2555 个 miRNA 序列。我们比较了 BrS 患者和对照组之间的 miRNA 表达。我们使用 RT-PCR 验证了这些 miRNA 在筛查队列中是否显著上调或下调。我们还纳入了 72 名日本 BrS 患者和 56 名对照进行这些 miRNA 的复制。
8 个 miRNA（hsa-miR-223-3p、hsa-miR-22-3p、hsa-miR-221-3p、hsa-miR-4485-5p、hsa-miR-550a-5p、hsa-miR-423-3p、hsa-miR-23a-3p 和 hsa-miR-30d-5p）下调，1 个 miRNA（hsa-miR-873-3p）上调超过 3 倍。多变量逻辑回归分析确定 hsa-miR-423-3p、hsa-miR-223-3p 和 hsa-miR-23a-3p 与 BrS 独立相关（P < 0.0001）。基于交叉验证的 AUC 为 0.871，灵敏度和特异性分别为 83.5%和 81.1%。
血浆 miRNAs 是 BrS 的潜在非侵入性生物标志物，构建的逻辑模型可用于区分 BrS。
