Abstract
Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) may alter miRNA transcription, maturation and target specificity, thus affecting stroke susceptibility. We aimed to investigate whether miR-200b and miR-495 SNPs may be associated with ischemic stroke (IS) risk and further explore underlying mechanisms including related genes and pathways. MiR-200b rs7549819 and miR-495 rs2281611 polymorphisms were genotyped among 712 large-artery atherosclerosis (LAA) stroke patients and 1,076 controls in a case–control study. Bioinformatic analyses were performed to explore potential association of miR-200b/495 with IS and to examine the effects of these two SNPs on miR-200b/495. Furthermore, we evaluated the association between these two SNPs and stroke using the public GWAS datasets. In our case–control study, rs7549819 was significantly associated with a decreased risk of LAA stroke (OR = 0.73, 95% CI = 0.58–0.92; p = 0.007), while rs2281611 had no significant association with LAA stroke risk. These results were consistent with the findings in East Asians from the GIGASTROKE study. Combined effects analysis revealed that individuals with 2–4 protective alleles (miR-200bC and miR-495 T) exhibited lower risk of LAA stroke than those with 0–1 variants (OR = 0.76, 95% CI = 0.61–0.96; p = 0.021). Bioinformatic analyses showed that miR-200b and miR-495 were significantly associated with genes and pathways related to IS pathogenesis, and rs7549819 and rs2281611 markedly influenced miRNA expression and structure. MiR-200b rs7549819 polymorphism and the combined genotypes of miR-200b rs7549819 and miR-495 rs2281611 polymorphisms were associated with decreased risk of LAA stroke in Chinese population.
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Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. The GIGASTROKE GWAS dataset across ancestries and stroke subtypes is available in the GWAS Catalog (GCST90104534–GCST90104563). The MEGASTROKE GWAS dataset is available from http://www.megastroke.org/index.html.
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Acknowledgements
We thank Zhanyun Ren of Yixing Hospital affiliated to Jiangsu University and Changying Chen of Nanjing Medical University for sample and data collection. We also thank GIGASTROKE Consortium and MEGASTROKE Consortium for providing summary data.
Funding
This work was supported by National Natural Science Foundation of China (Grant numbers 81771285, U20A20357 and 81870946).
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Shanmei Qin: Conceptualization; formal analysis; writing–original draft. Chong Shen: Data curation; resources. Wuzhuang Tang: Data curation; resources. Mengmeng Wang: Writing–review and editing. Ying Lin: Data curation. Zhaojun Wang: Data curation. Yunzi Li: Data curation. Zhizhong Zhang: Conceptualization; supervision; writing–review and editing; funding acquisition. Xinfeng Liu: Conceptualization; supervision; writing–review and editing; funding acquisition.
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This study was approved by the Ethics Review Board of the local participating hospitals (2017NZGKJ-041), and written informed consent was obtained from all participants prior to the investigation.
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Qin, S., Shen, C., Tang, W. et al. Impact of miR-200b and miR-495 variants on the risk of large-artery atherosclerosis stroke. Metab Brain Dis 38, 631–639 (2023). https://doi.org/10.1007/s11011-022-01119-w
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DOI: https://doi.org/10.1007/s11011-022-01119-w