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Genetic polymorphisms in lncRNAs predict recurrence of ischemic stroke

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Abstract

Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic biomarkers for the prediction of human complex diseases such as ischemic stroke (IS). However, so far, no reports have focused on the relationship of lncRNA polymorphisms with IS onset and prognosis. In our study, eight potential functional polymorphisms of four well-known lncRNAs (H19 rs2107425 and rs2251375, MALAT1 rs4102217 and rs3200401, MEG3 rs11160608 and rs4081134, SENCR rs4526784 and rs555172) were genotyped in 657 ischemic stroke patients. Then, the association between lncRNA polymorphisms and IS onset and recurrence were investigated. These lncRNA variants were not associated with age onset of IS. However, we observed that MEG3 rs4081134 AA genotype was statistically related with a reduced risk of stroke recurrence, particularly for patients with large-artery atherosclerotic stroke. Also, the decreased risk was more prominent in elders, non-smokers, non-drinkers and hypertensive patients. Furthermore, the variant genotype AA of rs4081134 was an independent predictor for IS recurrence using the multivariate Cox regression model. Our findings indicated that MEG3 rs4081134 can serve as a useful biomarker and potential therapeutic target in IS recurrence. More researches are needed to verify our results and explore the underlying molecular mechanisms.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

lncRNAs:

Long non-coding RNAs

MRI:

Magnetic resonance imaging

CT:

Computed tomography

SVO:

Small-vessel occlusion

LAA:

Large-artery atherosclerosis

PCR-LDR:

Polymerase chain reaction-ligase detection reaction method

HR:

Hazard ratio

CI:

Confidence interval

References

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81400950, 81501006), Natural Science Foundation of Liaoning Province (Grant No. 2019-MS-365, 2019-MS-364).

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Authors and Affiliations

Authors

Contributions

XL was responsible for the original concept and the overall design of the research. TLX, YTZ, and QWW collected the clinical data and sample. RXZ, TLX and YTZ carried the experiments and analyzed the data. RXZ and XL wrote and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xu Liu.

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Ethics approval and consent to participate

The program adhered to guidelines of patients’ consent for participation and research and was supported by the Ethics Committee of First Affiliated Hospital of China Medical University (No. 2014(50)).

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Supplementary Information

Table S1

Primer sequences and probes of lncRNA polymorphisms. (PDF 168 kb)

Figure S1

Allele frequency distributions of lncRNA polymorphisms among different populations. (PDF 229 kb)

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Zhu, R., Xiao, T., Wang, Q. et al. Genetic polymorphisms in lncRNAs predict recurrence of ischemic stroke. Metab Brain Dis 36, 1353–1359 (2021). https://doi.org/10.1007/s11011-021-00725-4

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  • DOI: https://doi.org/10.1007/s11011-021-00725-4

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