OBJECTIVE Venous thrombosis (VT) is a complex condition with a highly heritable genetic component that predisposes one to its development. Certain microRNAs (miRNAs) might be used as biomarkers of VT, but few studies have examined miRNA expression in this respect. The aim of the present work was to identify a plasma miRNA profile associated with VT. Approach and Results: miRNAs were analyzed by quantitative polymerase chain reaction in plasma samples from members of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) population (n=935). A discovery phase involving the screening of 752 miRNAs from a subset of 104 GAIT-2 subjects was followed by an internal validation phase in which the selected miRNAs were quantified in the whole GAIT-2 population. In the discovery phase, 16 miRNAs were selected, including 9 associated with VT and 7 that correlated with an intermediate phenotype of VT. In the next phase, 4 miRNAs were validated as differentially expressed (false discovery rate, <0.1) in VT: hsa-miR-126-3p, hsa-miR-885-5p, hsa-miR-194-5p, and hsa-miR-192-5p. The 4 miRNAs each returned a significant (P<0.05) odds ratio for VT (range of 1.3-1.8). A risk model including the 4 miRNAs, age, and sex returned an area under the receiver operating characteristic curve of 0.77. Moreover, all 4 miRNAs showed significant correlations with intermediate phenotypes of VT (eg, protein S and factor VII). The targets of the miRNAs in the blood coagulation pathway and their interactions are also discussed. CONCLUSIONS The present results suggest a 4-miRNA plasma profile associated with VT is of potential use in predicting the risk of this condition.

中文翻译：

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与静脉血栓形成相关的血浆MicroRNA谱的鉴定。

目的静脉血栓形成（VT）是一种复杂的疾病，具有高度可遗传的遗传成分，因此容易导致其发展。某些microRNA（miRNA）可以用作VT的生物标志物，但很少有研究检查过这方面的miRNA表达。本工作的目的是确定与VT相关的血浆miRNA图谱。方法和结果：通过定量聚合酶链反应在来自GAIT-2（特发性血友病2的基因分析）人群（n = 935）的血浆样品中分析了miRNA。一个发现阶段涉及从104名GAIT-2受试者的一个子集中筛选752个miRNA，随后是内部验证阶段，其中选定的miRNA在整个GAIT-2群体中进行定量。在发现阶段，选择了16个miRNA，包括与VT相关的9个和与VT的中间表型相关的7个。在下一阶段，验证了4种miRNA在VT中的差异表达（错误发现率，<0.1）：hsa-miR-126-3p，hsa-miR-885-5p，hsa-miR-194-5p和hsa- miR-192-5p。4个miRNA各自对VT返回显着（P <0.05）的优势比（范围为1.3-1.8）。包含4种miRNA，年龄和性别的风险模型在接受者操作特征曲线下的面积为0.77。此外，所有4个miRNA均与VT的中间表型（例如蛋白S和VII因子）显着相关。还讨论了miRNA在凝血途径中的靶标及其相互作用。结论目前的结果表明，与VT相关的4-miRNA血浆谱在预测这种疾病的风险方面具有潜在的用途。