Shinya Yuki, Miyawaki Satoru, Imai Hideaki, Hongo Hiroki, Ono Hideaki, Takenobu Atsumi, Nakatomi Hirofumi, Teraoka Akira, Saito Nobuhito
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Neurosurgery, Teraoka Memorial Hospital, Fukuyama, Hiroshima, Japan.
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
J Stroke Cerebrovasc Dis. 2017 Nov;26(11):2638-2644. doi: 10.1016/j.jstrokecerebrovasdis.2017.06.043. Epub 2017 Aug 7.
Intracranial atherosclerosis of the anterior circulation (anterior ICAS) and intracranial atherosclerosis of the posterior circulation (posterior ICAS) are thought to involve different pathogeneses and risk factors. Recently, we identified a genetic variant that has a significant association with ICAS. The variant was ring finger protein 213 (RNF213) c.14576G>A (rs112735431), which was originally identified as a susceptibility genetic variant for moyamoya disease (MMD). The present study investigated the association of RNF213 c.14576G>A with anterior and posterior ICAS.
A total of 221 study participants (43 with anterior ICAS, 61 with posterior ICAS, 12 with extracranial carotid atherosclerosis [ECAS], 5 with MMD, and 100 control subjects) were recruited from April 2015 to October 2015. A genetic analysis of RNF213 c.14576G>A and an association study with these cerebrovascular diseases were performed.
RNF213 c.14576G>A was present in 10 of 43 patients in the anterior ICAS group and 4 of 5 patients in the MMD group, but was not present in the patients in the posterior ICAS and ECAS groups. c.14576G>A was found in 2 of 100 patients in the control group. RNF213 c.14576G>A showed a significant association with anterior ICAS (allele count: P = 3.9 × 10, odds ratio [OR] = 13.0, 95% confidence interval [CI] = 2.8-60.8; prevalence of carriers of c.14576G>A: P = 2.6 × 10, OR = 14.8, 95% CI = 3.1-71.3). However, RNF213 c.14576G>A showed no association with posterior ICAS. RNF213 c.14576G>A also had a significant association with MMD and had no association with ECAS.
The genetic variant RNF213 c.14576G>A is significantly associated with anterior ICAS but not with posterior ICAS. The present findings may indicate factors involved in the pathogenesis of ICAS-related stroke.
前循环颅内动脉粥样硬化（前循环颅内动脉粥样硬化，anterior ICAS）和后循环颅内动脉粥样硬化（后循环颅内动脉粥样硬化，posterior ICAS）被认为涉及不同的发病机制和危险因素。最近，我们鉴定出一种与颅内动脉粥样硬化显著相关的基因变异。该变异为环指蛋白213（RNF213）c.14576G>A（rs112735431），最初被鉴定为烟雾病（MMD）的易感性基因变异。本研究调查了RNF213 c.14576G>A与前循环和后循环颅内动脉粥样硬化的相关性。
2015年4月至2015年10月共招募了221名研究参与者（43例前循环颅内动脉粥样硬化患者、61例后循环颅内动脉粥样硬化患者、12例颅外颈动脉粥样硬化[ECAS]患者、5例烟雾病患者和100名对照者）。对RNF213 c.14576G>A进行基因分析，并与这些脑血管疾病进行关联研究。
前循环颅内动脉粥样硬化组43例患者中有10例存在RNF213 c.14576G>A，烟雾病组5例患者中有4例存在该变异，但后循环颅内动脉粥样硬化组和颅外颈动脉粥样硬化组患者中未发现该变异。对照组100例患者中有2例存在c.14576G>A。RNF213 c.14576G>A与前循环颅内动脉粥样硬化显著相关（等位基因计数：P = 3.9×10，优势比[OR] = 13.0，95%置信区间[CI] = 2.8 - 60.8；c.14576G>A携带者患病率：P = 2.6×10，OR = 14.8，95% CI = 3.1 - 71.3）。然而，RNF213 c.14576G>A与后循环颅内动脉粥样硬化无相关性。RNF213 c.14576G>A也与烟雾病显著相关，与颅外颈动脉粥样硬化无相关性。
基因变异RNF213 c.14576G>A与前循环颅内动脉粥样硬化显著相关，但与后循环颅内动脉粥样硬化无关。本研究结果可能提示了颅内动脉粥样硬化相关卒中发病机制中的相关因素。
