CircRNAs belong to a novel class of noncoding RNAs that are generated by exons of genes by alternative mRNA splicing and involved in pathophysiological processes of ischemic stroke by regulating neuro-inflammation. A total of 982 patients were enrolled in our study for stroke recovery analysis. The aim of our study was to first explore the association between the inflammation-related circRNA polymorphism and functional outcome 3 months after ischemic stroke by using multivariate logistic regression model. Next, we further investigated the role of circRNA polymorphism in predicting stroke recurrence by using Cox proportional hazard regression model. Five circRNA polymorphisms were genotyped by using polymerase chain reaction and ligation detection reaction method. We identified circ-STAT3 (signal transducer and activator of transcription) rs2293152 GG genotype to be associated with poorer recovery 90 days after stroke (OR = 1.452, 95% CI: 1.165–4.362, p = 0.016). After adjusting for confound factors, the association for rs2293152 with 3 months outcome after IS was stronger, suggesting a mechanism that rs2293152 is an independent risk factor for stroke recovery (OR = 2.255, 95% CI: 1.034–2.038, p = 0.031). However, no other circRNA polymorphisms (circ-DLGAP4 rs41274714, circ-TRAF2 rs10870141, circ-ITCH rs10485505, rs4911154) were associated with functional outcome 3 months after stroke in any genetic models. Subgroup analysis revealed that the negative effect of rs2293152 GG genotype was greater in female and older patients, subjects with history of hypertension. Additionally, all the circRNA polymorphisms were not correlated with recurrent risk of ischemic stroke. Our results indicated that circ-STAT3 might be a novel biomarker for predicting functional outcome after stroke and an important contributor to the ischemic stroke recovery.

CircRNAs 属于一类新型非编码 RNAs，由基因外显子通过选择性 mRNA 剪接产生，并通过调节神经炎症参与缺血性卒中的病理生理过程。我们的研究共招募了 982 名患者进行中风恢复分析。我们研究的目的是首先使用多变量逻辑回归模型探索炎症相关的circRNA多态性与缺血性卒中3个月后功能结果之间的关联。接下来，我们使用 Cox 比例风险回归模型进一步研究了 circRNA 多态性在预测卒中复发中的作用。采用聚合酶链式反应和连接检测反应法对5个circRNA多态性进行基因分型。p  = 0.016）。调整混杂因素后，rs2293152 与 IS 后 3 个月结果的相关性更强，表明 rs2293152 是卒中恢复的独立危险因素的机制（OR = 2.255, 95% CI: 1.034–2.038, p = 0.031)。然而，在任何遗传模型中，没有其他 circRNA 多态性（circ-DLGAP4 rs41274714、circ-TRAF2 rs10870141、circ-ITCH rs10485505、rs4911154）与中风后 3 个月的功能结果相关。亚组分析显示，rs2293152 GG 基因型的负面影响在有高血压病史的女性和老年患者中更大。此外，所有 circRNA 多态性均与缺血性卒中的复发风险无关。我们的研究结果表明，circ-STAT3 可能是预测卒中后功能结果的新型生物标志物，并且是缺血性卒中恢复的重要因素。