Khurana Vini G, Meissner Irene, Meyer Fredric B
Department of Neurologic Surgery, and the Mayo Stroke Center, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Neurosurg Focus. 2004 Nov 15;17(5):E7. doi: 10.3171/foc.2004.17.5.7.
Anecdotal evidence exists for at least two subpopulations of intracranial saccular aneurysms; those that form rapidly and rupture when small and those that enlarge slowly and are particularly prone to rupture when they are 10 mm or more in diameter. The goal in this study was to determine if there was genetic evidence to support the classification of intracranial saccular aneurysms as 'rupture-prone' or 'rupture-resistant' lesions.
The authors prospectively obtained and analyzed clinical and genetic data in a cohort of 197 individuals composed of 58 patients with ruptured intracranial saccular aneurysms, 49 with unruptured aneurysms, and 90 healthy community volunteers. Based on recent studies supporting an increasingly relevant role for the critical vasomodulatory protein endothelial nitric oxide synthase (eNOS) in aneurysm pathobiology, the authors assayed blood from all 197 participants to determine and compare their eNOS genotypes. The eNOS gene intron 4 27-base pair variable-number tandem-repeat polymorphism was significantly overrepresented in persons with ruptured intracranial saccular aneurysms compared with community volunteers (p < 0.002). When comparing eNOS genotypes among patients with ruptured or unruptured aneurysms, an approximately 10-fold increase in the odds of presenting with brain aneurysm rupture was found among individuals with multiple variant eNOS alleles (p = 0.004).
Uniquely, the authors have identified a set of eNOS gene variations whose presence indicates patients with intracranial saccular aneurysms that are more prone to rupture. The authors conclude that if these findings are reproducible in the setting of a large multicenter study, then in addition to known anatomical factors, a rapid and costeffective genetic screening tool will become available to clinicians as an aid to predicting rupture risks in patients presenting with unruptured intracranial aneurysms.
关于颅内囊状动脉瘤至少存在两个亚群的传闻证据；一类是形成迅速且在较小的时候就破裂的动脉瘤，另一类是缓慢增大且在直径达到10毫米或更大时特别容易破裂的动脉瘤。本研究的目的是确定是否有遗传证据支持将颅内囊状动脉瘤分类为“易破裂”或“抗破裂”病变。
作者前瞻性地获取并分析了197名个体的临床和遗传数据，该队列包括58例颅内囊状动脉瘤破裂患者、49例未破裂动脉瘤患者和90名健康社区志愿者。基于近期研究支持关键血管调节蛋白内皮型一氧化氮合酶（eNOS）在动脉瘤病理生物学中发挥越来越重要的作用，作者对所有197名参与者的血液进行检测，以确定并比较他们的eNOS基因型。与社区志愿者相比，颅内囊状动脉瘤破裂患者中eNOS基因内含子4的27个碱基对可变数目串联重复多态性明显过多（p < 0.002）。在比较破裂或未破裂动脉瘤患者的eNOS基因型时，发现具有多个变异eNOS等位基因的个体发生脑动脉瘤破裂的几率增加了约10倍（p = 0.004）。
独特的是，作者已经鉴定出一组eNOS基因变异，其存在表明颅内囊状动脉瘤患者更容易破裂。作者得出结论，如果这些发现在大型多中心研究中可重复，那么除了已知的解剖学因素外，临床医生将可获得一种快速且经济高效的基因筛查工具，以帮助预测未破裂颅内动脉瘤患者的破裂风险。
