Abstract
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.
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We are deeply grateful to all participants of this study.
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This study was supported by Natural Science Foundation of Liaoning province of China (2019-MS-364) and the National Natural Science Foundation of China (81501006).
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Designed the experiments: Ruixia Zhu, Xu Liu; performed the experiments: Ruixia Zhu, Xu Liu, Jingjing Zhao; analyzed the data: Xu Liu, Qianwen Wang, Hongtao Chang; wrote the paper: Ruixia Zhu, Qianwen Wang.
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This study was approved by the ethics committee of the First Affiliated Hospital of China Medical University approval, in accordance with the principles of the Helsinki Declaration (AF-SOP-07–1.0–01). Written informed consents were obtained from all the participants.
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Liu, X., Wang, Q., Zhao, J. et al. Inflammation-Related circRNA Polymorphism and Ischemic Stroke Prognosis. J Mol Neurosci 71, 2126–2133 (2021). https://doi.org/10.1007/s12031-021-01889-5
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DOI: https://doi.org/10.1007/s12031-021-01889-5