A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis.
A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis.
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DOI：
10.1371/journal.pone.0156607
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hong SC
中科院分区：
文献类型：
--
作者：
Bang OY;Chung JW;Cha J;Lee MJ;Yeon JY;Ki CS;Jeon P;Kim JS;Hong SC
颅内动脉粥样硬化性狭窄（ICAS）和烟雾病（MMD）在亚洲人中很常见。我们假设环指蛋白213基因多态性（RNF 213）是东亚人MMD的易感基因，也是经常规血管造影（无基底侧支）和高分辨率MRI（HR-MRI，存在斑块）确诊的患者ICAS的易感基因。我们分析了532例大脑中动脉（MCA）分布缺血事件和颈内动脉远端或MCA近端相关狭窄病变的连续患者，但没有明显的颈动脉或心脏栓塞来源。对370例（69.5%）患者进行了额外的血管造影，对283例（53.2%）患者进行了HR-MRI。根据血管造影和HR-MRI结果，234例患者被诊断为ICAS，288例患者被诊断为MMD。在50例（21.4%）ICAS患者和119例（69.1%）MMD患者中观察到RNF 213变异体。在25.2%经HR-MRI证实的ICAS患者中观察到该变异。类似地，15.8%的通过血管造影排除MMD的ICAS患者具有这种变异。在ICAS患者中，RNF 213变异携带者比非携带者更年轻，更可能有MMD家族史。多变量检验显示，只有ICAS发病年龄与RNF 213变异独立相关（优势比，0.97; 95%CI，0.944-0.99）。RNF 213不仅是MMD的易感基因，也是东亚人ICAS的易感基因。需要对东亚人群以外的ICAS患者的RNF 213变异进行进一步研究。
Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944–0.99). RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations.