Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci.
Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci.
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DOI：
10.1161/strokeaha.116.013869
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发表时间：
2016-12
期刊：
影响因子：
8.3
通讯作者：
Sharp FR
中科院分区：
文献类型：
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作者：
Dykstra-Aiello C;Jickling GC;Ander BP;Shroff N;Zhan X;Liu D;Hull H;Orantia M;Stamova BS;Sharp FR
虽然外周血mRNA和microRNA在缺血性中风后发生变化，但长链非编码RNA（lncRNA）的任何作用尚不清楚，lncRNA构成了大部分基因组，并与各种疾病有关。因此，我们假设lncRNA表达也在中风后发生变化。在266个全血RNA样本中评估lncRNA表达，每个样本从缺血性卒中患者和匹配的血管危险因素对照中抽取一次。通过协方差分析（ANCOVA，p值< 0.005;倍数变化> 0.005）评估差异lncRNA表达。|1.2|）、主成分分析和层次聚类，并在验证集（n=90）上进行验证。使用具有混杂因子校正的ANCOVA评估中风后时间lncRNA表达变化（p<0.005;与事件发生后的时间的部分相关性>| 0.4|).由于中风中存在性别二态性，因此分别对每种性别进行分析。299个lncRNA在中风和对照男性之间差异表达，而97个lncRNA在中风和对照女性之间差异表达。在男性和女性中分别检测到49种和31种lncRNA表达随卒中后时间的显著变化。一些差异表达的lncRNA定位于先前确定的推定中风风险基因的基因组位置附近，包括脂蛋白、Lp（A）样2、ABO血型、前列腺素12合酶和α-内收蛋白。这项研究提供了证据，改变和性别二态性lncRNA表达在中风患者的外周血相比，对照组，并表明lncRNA有潜力中风生物标志物的发展。一些受调节的lncRNA可以调节一些先前确定的推定的中风风险基因。
Though peripheral blood mRNA and microRNA change following ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes following stroke. lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from ischemic stroke patients and matched vascular risk factor controls. Differential lncRNA expression was assessed by Analysis of Covariance (ANCOVA, p-value < 0.005; fold change > |1.2|), principal components analysis and hierarchical clustering on a derivation set (n=176) and confirmed on a validation set (n=90). Post-stroke temporal lncRNA expression changes were assessed using ANCOVA with confounding factor correction (p<0.005; partial correlation with time since event >|0.4|). Because sexual dimorphism exists in stroke, analyses were performed for each sex separately. 299 lncRNAs were differentially expressed between stroke and control males, whereas 97 lncRNAs were differentially expressed between stroke and control females. Significant changes of lncRNA expression with time after stroke were detected for 49 lncRNAs in males and 31 lncRNAs in females. Some differentially expressed lncRNAs mapped close to genomic locations of previously identified putative stroke-risk genes, including Lipoprotein, Lp(A)-Like 2, ABO blood group, Prostaglandin 12 Synthase, and α-Adducins. This study provides evidence of altered and sexually dimorphic lncRNA expression in peripheral blood of stroke patients compared to controls and suggests lncRNAs have potential for stroke biomarker development. Some regulated lncRNA could regulate some previously identified putative stroke-risk genes.