Epidemiology and genetics of intracranial aneurysms
Epidemiology and genetics of intracranial aneurysms
复制标题
DOI：
10.1016/j.ejrad.2012.12.026
复制
发表时间：
2013-10-01
影响因子：
3.3
通讯作者：
Muto, M.
中科院分区：
文献类型：
--
作者：
Caranci, F.;Briganti, F.;Muto, M.
颅内动脉瘤是获得性病变（占人口的5 - 10%），其中一小部分破裂导致蛛网膜下腔出血，造成毁灭性后果。到目前为止，颅内动脉瘤形成的确切病因尚不清楚。与未破裂的颅内动脉瘤的患病率相比，蛛网膜下腔出血的发生率较低，这表明绝大多数颅内动脉瘤不会破裂，在确定最佳管理方面很重要。预测破裂的最重要因素是动脉瘤的大小和部位，除了环境因素（吸烟、过量饮酒和高血压）外，流行病学研究表明，颅内动脉瘤的发病机制也有一个常见的影响因素，蛛网膜下腔出血患者的一级和二级亲属中发生率增加。与散发性动脉瘤相比，家族性动脉瘤往往更大，更常位于大脑中动脉，更可能是多发性的。除了常见的发生，还有几种与颅内动脉瘤形成相关的遗传性疾病，包括常染色体显性遗传性多囊肾病，神经纤维瘤病I型，马凡综合征，多发性内分泌瘤I型，弹性假黄瘤，遗传性出血性毛细血管扩张症，和Ehlers-Danlos综合征II型和IV型。家族性发生和与遗传性疾病的相关性表明遗传因素可能在颅内动脉瘤的发展中起作用。在患有颅内动脉瘤的家族和同胞对中的广泛连锁研究已经鉴定了染色体上的几个基因座，特别是在染色体1p34.3-p36.13、7q11、19q13.3和Xp22上。1p34.3-p36.13和7q11上的基因座与位置候选基因有中度正相关（串珠素基因、弹性蛋白基因、1型胶原A2基因）。此外，在2个基因中分析的3个多态性（内皮型一氧化氮合酶T786 C、白细胞介素-6 G572 C和白细胞介素-6 G174 C）与破裂/未破裂动脉瘤显著相关：内皮型一氧化氮合酶基因单核苷酸多态性增加了风险，而IL-6 G174C似乎具有保护作用。最近，两个基因组基因座（内皮素受体A和细胞周期蛋白依赖性激酶抑制剂2BAS）与日本人群的颅内动脉瘤显著相关;内皮素-1是由内皮细胞产生的有效的血管收缩剂。直到现在，没有针对特定遗传风险因素的诊断测试来识别处于发展颅内动脉瘤的高风险的患者。遗传决定因素可能是有用的，以便提供阻止动脉瘤形成的线索，并获得用于识别风险增加的个体的诊断工具。必须进行进一步的多中心研究。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Intracranial aneurysms are acquired lesions (5-10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences.Until now, the exact etiology of intracranial aneurysms formation remains unclear.The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site.In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first-and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple.Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV.The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms.Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3-p36.13, 7q11, 19q13.3, and Xp22.For the loci on 1p34.3-p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2 gene).Moreover, 3 of the polymorphisms analyzed in 2 genes (endothelial nitric oxide synthase T786C, interleukin-6 G572C, and interleukin-6 G174C) were found to be significantly associated with ruptured/unruptured aneurysms: the endothelial nitric oxide synthase gene single-nucleotide polymorphisms increased the risk, while IL-6 G174C seemed protective.More recently, two genomic loci (endothelin receptor A and cyclin-dependent kinase inhibitor 2BAS) have been found to be significantly associated with intracranial aneurysms in the Japanese population; endothelin-1 is a potent vasoconstrictor produced by the endothelial cells.Until now, there are no diagnostic tests for specific genetic risk factors to identify patients who are at a high risk of developing intracranial aneurysms.Knowledge of the genetic determinants may be useful in order to allow clues on stopping aneurysm formation and obtain diagnostic tools for identifying individuals at increased risk. Further multicenter studies have to be carried out. (C) 2013 Elsevier Ireland Ltd. All rights reserved.