Department of Medicine, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
J Neurol Sci. 2019 Dec 15;407:116526. doi: 10.1016/j.jns.2019.116526. Epub 2019 Oct 13.
Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine.
We searched the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Genome Wide Association Study (GWAS) catalog and PubMed for original research articles on genetic variants associated with SICH as of 15 June 2019 using the PRISMA guideline.
Eight hundred and sixty-four articles were identified using pre-specified search criteria, of which 64 met the study inclusion criteria. Among eligible articles, only 9 utilized GWAS approach while the rest were candidate gene studies. Thirty-eight genetic loci were found to be variously associated with the risk of SICH, hematoma volume, functional outcome and mortality, out of which 8 were from GWAS including APOE, CR1, KCNK17, 1q22, CETP, STYK1, COL4A2 and 17p12. None of the studies included indigenous Africans.
Given this limited information on the genetic contributors to SICH, more genomic studies are needed to provide additional insights into the pathophysiology of SICH, and develop targeted preventive and therapeutic strategies. This call for additional investigation of the pathogenesis of SICH is likely to yield more discoveries in the unexplored indigenous African populations which also have a greater predilection.
尽管自发性脑出血（SICH）具有高度遗传性，但目前尚无任何基于证据的疾病修饰治疗方法，仅有少数基因与之相关。非洲裔个体尤其容易发生 SICH，而非洲原住民的发病风险更高。我们系统地回顾了与 SICH 相关的遗传变异，并探讨了加速 SICH 基因组研究以实现精准医学的机会。
我们按照 PRISMA 指南，通过 NHGRI-EBI 基因组广泛关联研究（GWAS）目录和 PubMed，检索了截至 2019 年 6 月 15 日与 SICH 相关的遗传变异的原始研究文章，检索词为“spontaneous intracerebral hemorrhage”[MeSH Terms] 或“spontaneous intracerebral haemorrhage”[All Fields]。
使用预定义的搜索标准共确定了 864 篇文章，其中 64 篇符合研究纳入标准。在合格的文章中，只有 9 篇使用了 GWAS 方法，其余均为候选基因研究。共发现 38 个遗传位点与 SICH 的发病风险、血肿量、功能结局和死亡率存在不同程度的关联，其中 8 个来自 GWAS，包括 APOE、CR1、KCNK17、1q22、CETP、STYK1、COL4A2 和 17p12。没有一项研究纳入了非洲原住民。
鉴于目前对 SICH 遗传因素的了解有限，需要更多的基因组研究来提供更多关于 SICH 病理生理学的见解，并制定有针对性的预防和治疗策略。这一呼吁对 SICH 发病机制进行更多的研究，可能会在未被探索的非洲原住民群体中产生更多的发现，而这些群体的发病倾向更高。
