Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, China.
Mol Neurobiol. 2019 Feb;56(2):1330-1343. doi: 10.1007/s12035-018-1055-3. Epub 2018 Jun 8.
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.
缺血性脑卒中（IS）是一种死亡率和致残率高、治疗窗口有限的主要疾病。长期以来，人们一直在寻找用于早期诊断 IS 的生物标志物。家族和双胞胎研究证实，遗传变异在 IS 的发病机制中起着重要作用。除了先前通过遗传连锁分析发现的单基因 IS（孟德尔遗传）的 DNA 突变外，最近使用全基因组关联研究（GWAS）和 microRNA 表达谱分析的研究导致了大量多基因 IS（散发性 IS）的 DNA 和 microRNA 生物标志物，特别是在不同的 IS 亚型和影像学表型中。本综述总结了临床研究中发现的遗传标记，并讨论了它们在血管壁发育或再生异常、神经元凋亡、兴奋毒性死亡、炎症、神经发生和血管生成中涉及的致病分子机制。还讨论了环境对遗传学的可能影响。我们还对这些 IS 生物标志物的进一步研究和临床应用进行了展望。
