Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PLoS One. 2012;7(9):e44906. doi: 10.1371/journal.pone.0044906. Epub 2012 Sep 18.
MicroRNA (miRNA) has been found in human blood. It has been increasingly suggested that miRNAs may serve as biomarkers for diseases. We examined the potential of circulating miRNA to serve as predictors of atrial fibrillation (AF).
METHODOLOGY/PRINCIPAL FINDINGS: During the discovery stage of this project, we used massively parallel signature sequencing (MPSS) to carry out an in-depth analysis of the miRNA expression profile (miRNome) in 5 healthy controls, 5 patients with paroxysmal atrial fibrillation (PAF) alone, and 5 patients with persistent atrial fibrillation (PersAF) alone. Twenty-two specific miRNAs were found to be dysregulated in each PAF group, PersAF group, or control group. Four candidate microRNAs (miRNA-146a, miRNA-150, miRNA-19a, and miRNA-375) met our selection criteria and were evaluated in an independent cohort of 90 plasma samples using TaqMan miRNA quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We found miRNA-150 levels to be reduced by a factor of approximately 17 in PAF relative to controls and a factor of approximately 20 in PersAF relative to controls (P<.0001). Logistic regression analyses were carried out to evaluate the reduced miRNA-150 expression levels (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.5 to 3.57, P<0.001), age (OR 1.1, 95% CI 1.36 to 2.73, P<0.001), and Left atrial diameter (LAD) (OR 1.5, 95% CI 1.36 to 1.8, P<0.001). Each was independently associated with AF. Much of the identified target genes related to AF were part of the inflammatory response system. We found that plasma levels of CRP were negatively correlated with the plasma levels of miRNA-150.
CONCLUSIONS/SIGNIFICANCE: In summary, we firstly found that plasma miRNA-150 levels in from AF patients were substantially lower than that from healthy people. Circulating reduced miRNA-150 was significantly associated with AF.
微小 RNA(miRNA)已在人类血液中被发现。越来越多的证据表明,miRNA 可能作为疾病的生物标志物。我们研究了循环 miRNA 作为心房颤动(AF)预测因子的潜力。
方法/主要发现:在本项目的发现阶段,我们使用大规模平行签名测序(MPSS)对 5 名健康对照者、5 名阵发性心房颤动(PAF)患者和 5 名持续性心房颤动(PersAF)患者的 miRNA 表达谱(miRNome)进行了深入分析。在每个 PAF 组、PersAF 组或对照组中,有 22 种特定的 miRNA 被发现失调。四种候选 microRNA(miRNA-146a、miRNA-150、miRNA-19a 和 miRNA-375)符合我们的选择标准,并在 90 个血浆样本的独立队列中使用 TaqMan miRNA 定量逆转录-聚合酶链反应(qRT-PCR)进行评估。我们发现,与对照组相比,PAF 患者的 miRNA-150 水平降低了约 17 倍,与对照组相比,PersAF 患者的 miRNA-150 水平降低了约 20 倍(P<.0001)。进行逻辑回归分析以评估降低的 miRNA-150 表达水平(比值比 [OR] 1.96,95%置信区间 [CI] 1.5 至 3.57,P<.001)、年龄(OR 1.1,95%CI 1.36 至 2.73,P<.001)和左心房直径(LAD)(OR 1.5,95%CI 1.36 至 1.8,P<.001)。每个因素都与 AF 独立相关。许多与 AF 相关的鉴定靶基因都与炎症反应系统有关。我们发现 CRP 血浆水平与 miRNA-150 血浆水平呈负相关。
结论/意义:总之,我们首次发现 AF 患者的血浆 miRNA-150 水平明显低于健康人群。循环减少的 miRNA-150 与 AF 显著相关。