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Association Between Genetic Variants in the lncRNA–p53 Regulatory Network and Ischemic Stroke Prognosis

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Abstract

Long noncoding RNAs (lncRNAs) serve as regulators or effectors of the p53 regulatory pathway. The lncRNA–p53 regulatory network plays an important role in ischemia-induced apoptosis and may be important for post-stroke recovery. Eight genetic variants of p53-related lncRNAs were genotyped in 982 patients to explore the association of single nucleotide polymorphisms (SNPs) in the genes related to the p53 regulatory pathway with ischemic stroke (IS) prognosis in a northern Chinese population. Long- and short-term outcomes were assessed by stroke recurrence and modified Rankin Scale score 3 months after stroke, respectively. We first identified that p53 rs1042522 and LINC-ROR rs2027701 could be associated with IS recurrence risk. On further cumulative effect analysis, we found that these two polymorphisms could jointly be associated with IS recurrence. Patients carrying 2–4 risk alleles showed a significantly higher IS recurrence risk than those harboring no or a single risk allele. In contrast to rs2027701 and rs1042522, the other SNPs were not associated with IS recurrence. Subsequently, we found that TUG1 rs2240183 CC genotype was associated with a favorable IS outcome after adjusting for confounding factors. However, the other seven genetic variants of p53-related lncRNAs were not associated with a functional outcome after stroke. p53 rs1042522 and LINC-ROR rs2027701 may exert combined effects on IS recurrence, and TUG1 rs2240183 may be a new biomarker to predict short-term IS outcomes as it modulates p53-mediated apoptosis.

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Data Availability

The data used in our study are available from the authors on reasonable request.

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.

Abbreviations

IS:

Ischemic stroke

lncRNAs:

Long noncoding RNAs

PVT1:

Plasmacytoma variant translocation 1

MALATI:

Metastasis associated lung adenocarcinoma transcript 1

MDM2:

Murine double minute 2

TUGI:

Taurine upregulated gene 1

LINC-ROR:

Regulator of reprogramming

NIHSS:

National Institute of Health Stroke Scale

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Acknowledgements

We are deeply grateful to all the participants of this study.

Funding

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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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Xu Liu, Lu Wang, Qianwen Wang, Jingjing Zhao, Hongtao Chang & Ruixia Zhu

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  1. Xu Liu
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  2. Lu Wang
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  3. Qianwen Wang
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  4. Jingjing Zhao
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  5. Hongtao Chang
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  6. Ruixia Zhu
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Contributions

Designed the experiments: Ruixia Zhu. Performed the experiments: Ruixia Zhu, Xu Liu, Jingjing Zhao. Analyzed the data: Xu Liu, Qianwen Wang, Hongtao Chang; Lu Wang. Wrote the paper: Ruixia Zhu ,Qianwen Wang. Revised the paper: Lu Wang.

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Correspondence to Ruixia Zhu.

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Liu, X., Wang, L., Wang, Q. et al. Association Between Genetic Variants in the lncRNA–p53 Regulatory Network and Ischemic Stroke Prognosis. Neurotox Res 39, 1171–1180 (2021). https://doi.org/10.1007/s12640-021-00357-7

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  • DOI: https://doi.org/10.1007/s12640-021-00357-7

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