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Influence of the rs6736 Polymorphism on Ischemic Stroke Susceptibility in Han Chinese Individuals via the Disruption of miR-7–1 Binding to the C14orf119 Gene

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Abstract

This study investigates the association between the C14orf119 gene rs6736 polymorphism and ischemic stroke (IS) susceptibility, and explores the influence of the rs6736 polymorphism on the binding between miR-7–1 and the C14orf119 gene. mRNA expression levels were determined in 45 IS patients and 45 matched controls via real-time quantitative PCR. A total of 774 IS patients and 793 matched controls were recruited from a Han Chinese population for genotyping, performed with the Sequenom MassARRAY iPLEX platform. A dual-luciferase reporter assay was used for the analysis of miRNA–mRNA binding. The results showed that the mRNA expression of C14orf119 differed significantly between IS patients and controls (t =  −2.235, P = 0.030). Significant associations were noted between the C14orf119 gene rs6736 polymorphism and IS susceptibility in Han Chinese individuals under the additive model [ORadj (95% CI) = 0.87 (0.76–1.00) Padj = 0.048] and dominant model [ORadj (95% CI) = 0.76 (0.61–0.94), Padj = 0.014], with adjustment for age and sex. Mutations in the rs6736 polymorphism disrupted the binding of miR-7–1 and the C14orf119 gene. The results of this study show that the rs6736 polymorphism in the 3′-untranslated region of the C14orf119 gene not only is associated with IS but also modifies the binding between miR-7–1 and the C14orf119 gene. The C14orf119 gene may participate in the relationship between IS and miR-7–1.

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Funding

This study is supported by the General Programs of the National Natural Science Foundation of China (NSFC, No. 81573756 and No. 81473670), and the Guangxi Natural Science Foundation Project (No. 2018GXNSFAA281224 and No. 2017GXNSFDA198013).

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Contributions

Authors L. Su and L. Gu designed the study and wrote the protocol. Authors X. Guo, L. Zhu, X. Zhao, and X. Wu undertook the statistical analysis and wrote the first draft of the manuscript. Authors J. Yang and J. Huang managed the literature searches and analyses. All authors contributed to and approved the final manuscript.

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Correspondence to Li Su.

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This study was approved by the ethics committees of the First Affiliated Hospital of Guangxi University of Chinese Medicine.

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Informed consent was obtained from both IS patients and controls.

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Not applicable.

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All authors declare that they have no conflicts of interest.

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Guo, X., Zhu, L., Zhao, X. et al. Influence of the rs6736 Polymorphism on Ischemic Stroke Susceptibility in Han Chinese Individuals via the Disruption of miR-7–1 Binding to the C14orf119 Gene. J Mol Neurosci 72, 459–467 (2022). https://doi.org/10.1007/s12031-021-01895-7

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  • DOI: https://doi.org/10.1007/s12031-021-01895-7

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