Sánchez van Kammen Mayte, Moomaw Charles J, van der Schaaf Irene C, Brown Robert D, Woo Daniel, Broderick Joseph P, Mackey Jason S, Rinkel Gabriël J E, Huston John, Ruigrok Ynte M
Department of Neurology and Neurosurgery, University Medical Centre Utrecht, Utrecht, the Netherlands.
Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
PLoS One. 2018 Jan 29;13(1):e0191974. doi: 10.1371/journal.pone.0191974. eCollection 2018.
Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals.
We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis.
We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3). No association was found for the other three circle of Willis variations.
In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.
颅内动脉瘤在家族中更常出现在同一动脉区域。几个动脉瘤位置与特定的 Willis 环变异相关。我们研究了一级亲属中相同的 Willis 环变异是否比无亲缘关系的个体更易出现。
我们在两组独立的有家族性动脉瘤且≥2 名一级亲属有 MRA/CTA 上 Willis 环成像的家族中评估了四种 Willis 环变异（经典型、A1 不对称型、后交通动脉不完全型和胎儿循环型）。在每个（索引）家族中，我们确定与先证者有相同 Willis 环变异的一级亲属比例，并将其与随机选择的无亲缘关系（对照）家族中与索引家族先证者有相同 Willis 环变异的一级亲属比例进行比较。通过条件逻辑事件/试验模型比较索引家族和对照家族中的一致性。该分析模拟了 1001 次；我们报告中位数一致性、比值比（OR）和 95%置信区间（95%CI）。分别对两组进行分析，并通过荟萃分析一起分析。
我们发现索引家族中 Willis 环构型的总体一致性高于对照家族（荟萃分析，244 个家族：OR 2.2，95%CI 1.6 - 3.0），这主要归因于后交通动脉不完全型的一致性更高（荟萃分析：OR 2.8，95%CI 1.8 - 4.3）。未发现其他三种 Willis 环变异存在关联。
在两组独立的有家族性动脉瘤的家族中，后交通动脉不完全型变异在家族内部比家族之间更常出现，提示这种 Willis 环变异具有遗传性。进一步的研究应调查与 Willis 环形成相关的基因变异。
