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Monogenic, Polygenic, and MicroRNA Markers for Ischemic Stroke

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Abstract

Ischemic stroke (IS) is a leading disease with high mortality and disability, as well as with limited therapeutic window. Biomarkers for earlier diagnosis of IS have long been pursued. Family and twin studies confirm that genetic variations play an important role in IS pathogenesis. Besides DNA mutations found previously by genetic linkage analysis for monogenic IS (Mendelian inheritance), recent studies using genome-wide associated study (GWAS) and microRNA expression profiling have resulted in a large number of DNA and microRNA biomarkers in polygenic IS (sporadic IS), especially in different IS subtypes and imaging phenotypes. The present review summarizes genetic markers discovered by clinical studies and discusses their pathogenic molecular mechanisms involved in developmental or regenerative anomalies of blood vessel walls, neuronal apoptosis, excitotoxic death, inflammation, neurogenesis, and angiogenesis. The possible impact of environment on genetics is addressed as well. We also include a perspective on further studies and clinical application of these IS biomarkers.

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Funding

This work was supported by grants from the Bill and Melinda Gates Foundation (to X. W.), Grant/Award Number: 01075000191 and OPP1099070; the Brigham and Women’s Hospital BRI Fund to Sustain Research Excellence (to X. W.); the National Institutes of Health/National Institute of Neurological Disorders and Stroke (to X. W.), Grant/Award Number: NS055072; Adelson Medical Research Foundation (to L. B., Subcontractor X. W.); National Natural Science Foundation of China (to Z. Z.), Grant Number: 81344438.

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Authors and Affiliations

  1. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Wu Chen, Bharati Sinha, Nirav J. Patel, Ali M. Aziz-Sultan, Antonio E. Chiocca & Xin Wang

  2. Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, China

    Wu Chen & Yi Li

  3. Department of Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Bharati Sinha

  4. Department of Neurosurgery, Boston Children’s Hospital, F.M. Kirby Neurobiology Center for Life Science, Harvard Medical School, Boston, MA, 02115, USA

    Larry Benowitz

  5. Experimental Center, Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, China

    Qinhua Chen

  6. Department of Neurology, Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, China

    Zhenghong Zhang

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  1. Wu Chen
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  2. Bharati Sinha
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  5. Qinhua Chen
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  7. Nirav J. Patel
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  8. Ali M. Aziz-Sultan
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  9. Antonio E. Chiocca
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  10. Xin Wang
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Dr. Xin Wang is the first corresponding author and Dr. Wu Chen is the co-corresponding author.

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Chen, W., Sinha, B., Li, Y. et al. Monogenic, Polygenic, and MicroRNA Markers for Ischemic Stroke. Mol Neurobiol 56, 1330–1343 (2019). https://doi.org/10.1007/s12035-018-1055-3

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  • DOI: https://doi.org/10.1007/s12035-018-1055-3

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