Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden. ; Department of Neurology and Rehabilitation Medicine, Skane University Hospital, Lund, Sweden.
J Stroke. 2014 Sep;16(3):114-23. doi: 10.5853/jos.2014.16.3.114. Epub 2014 Sep 30.
Stroke genetics includes several topics of clinical interest, including (1) molecular genetic variations affecting risk of monogenic stroke syndromes; (2) molecular genetic variations affecting risk of common stroke syndromes, sometimes with specific effects on risk of specific main types of stroke or subtypes of ischemic and hemorrhagic stroke; (3) genetics of conditions associated with stroke risk e.g. white matter hyperintensities, atrial fibrillation and hypertension; (4) hereditary causes of familial aggregation of stroke; (5) epigenetic impact on protein expression during acute brain injury; (6) genetic influence on stroke recovery; and (7) pharmacogenetics. Genetic research methods include candidate gene studies; Genome Wide Association Studies; family studies; RNA and protein analyses; and advanced computer-aided analytical methods to detect statistically significant associations. Several methods that could improve our knowledge of stroke genetics are being developed e.g.: Exome content analysis; Next-generation sequencing; Whole genome sequencing; and Epigenetics. During 2012-2014, several Single Nucleotide Polymorphisms (SNPs) have been related to common ischemic stroke risk. Certain SNPs have been associated with risk of specific ischemic stroke subtypes such as large vessel disease and cardiac embolism, particular subtypes of intracerebral hemorrhage (ICH), especially lobar ICH, and with prognosis after ICH. Large international studies on stroke recovery and exome content are ongoing. Advanced mathematical models have been used to study how several SNPs can act together and increase stroke risk burden. Such efforts require large numbers of patients and controls, which is achieved by co-operation in large international consortia such as the International Stroke Genetics Consortium. This overview includes an introduction to genetics, stroke genetics in general, and different genetic variations that may influence stroke risk. It presents some of the latest reports on stroke genetics published in high impact journals. The role of pharmacogenetics, the current clinical situation, and future prospects will also be discussed.
中风遗传学包括几个临床关注的主题，包括（1）影响单基因中风综合征风险的分子遗传变异；（2）影响常见中风综合征风险的分子遗传变异，有时对特定类型中风或缺血性和出血性中风亚型的风险有特定影响；（3）与中风风险相关的条件的遗传学，例如脑白质高信号、心房颤动和高血压；（4）中风家族聚集的遗传性原因；（5）急性脑损伤期间蛋白质表达的表观遗传学影响；（6）中风恢复的遗传影响；以及（7）药物遗传学。遗传研究方法包括候选基因研究；全基因组关联研究；家族研究；RNA 和蛋白质分析；以及先进的计算机辅助分析方法来检测统计学上显著的关联。正在开发几种可以提高我们对中风遗传学认识的方法，例如：外显子组内容分析；下一代测序；全基因组测序；和表观遗传学。在 2012-2014 年期间，几个单核苷酸多态性（SNP）与常见的缺血性中风风险有关。某些 SNP 与特定缺血性中风亚型的风险相关，例如大血管疾病和心源性栓塞，特定类型的颅内出血（ICH），特别是脑叶 ICH，以及 ICH 后的预后。关于中风恢复和外显子组内容的大型国际研究正在进行中。先进的数学模型已被用于研究几个 SNP 如何协同作用并增加中风风险负担。这些努力需要大量的患者和对照组，这是通过国际中风遗传学联合会等大型国际联盟的合作来实现的。本综述包括遗传学简介、一般中风遗传学以及可能影响中风风险的不同遗传变异。它介绍了一些在高影响力期刊上发表的最新中风遗传学报告。还将讨论药物遗传学的作用、当前的临床情况和未来前景。
