脑动脉瘤(brain aneurysm)是脑动脉壁的局限性囊性扩张,它会导致致命的血管破裂,世界上每年患病的人数高达50万。一个国际科学家小组近日发现了3个与脑动脉瘤风险增加有关的染色体片段,在揭开脑动脉瘤奥秘的道路上迈出了关键性的一步。相关论文11月9日在线发表于《自然—遗传学》(Nature Genetics)。
出血性中风发生的中值年龄是50岁,而且通常并无预兆。在大多数案例中,这种中风会导致严重或致死的脑损伤。由于对内在机理缺乏了解,医生只能在病发后才能作出反应,而这时大部分伤害已经形成。美国新当选的副总统约瑟夫?拜登20年前曾患过此病,不过他幸存了下来,且将脑部受到的伤害控制到了最小程度。
在最新研究中,美国耶鲁大学医学院的Murat Gunel和日本、荷兰等国科学家一起,扫描了2000个患有颅内动脉瘤和8000个健康个体的基因组。研究人员发现了3个特殊的染色体片段,其上的普通遗传突变能显著增加脑动脉瘤的风险,从而导致中风。这些个体分别来自芬兰、荷兰以及日本,各个小组的检测结果相似,说明这些突变在不同的人群中均会增加患病风险。
新研究还表明,危险基因突变数的增加会加大患脑动脉瘤的风险,携带较多危险基因突变的个体患病风险是常人的3倍。
论文合著者、耶鲁大学医学院的Richard Lifton说:“这些发现提供了基础性的认识,帮助我们了解一些遗传和生化变化导致了这个破坏性的脑部疾病,同时也提供了希望——我们有可能在血管破裂发生前进行预防性的治疗。”(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Genetics,doi:10.1038/ng.240,Kaya Bilguvar,Murat Günel
Susceptibility loci for intracranial aneurysm in European and Japanese populations
Stroke is the world's third leading cause of death. One cause of stroke, intracranial aneurysm, affects 2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment1. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24–1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm2, 3, 4, 5. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells6, 7, 8, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role9. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.