medicina60巻3号

2023年03月発行

特集 令和の脳卒中ディベート10番勝負—脳卒中治療ガイドライン2021とその先を識る 読者の識りたいに応える

脳卒中の遺伝子研究—RNF213関連疾患

著者： 岡﨑周平¹

所属機関： ¹大阪大学大学院医学系研究科神経内科学

ページ範囲：P.590 - P.594

Point
◎RNF213遺伝子は，もやもや病の感受性遺伝子として発見され，日本では，もやもや病患者の80〜90％がRNF213 p.R4810K多型を有している一方で，健常人の1〜2％も本多型の保因者である．
◎RNF213蛋白は，ユビキチン化機能とATP分解能を有するE3ユビキチンリガーゼで，標的となるさまざまな蛋白質をユビキチン化することで，炎症反応，抗菌活性，脂質代謝などのシグナル伝達経路を調整していると考えられている．
◎RNF213遺伝子多型は，もやもや病だけでなく，頭蓋内動脈狭窄症や，アテローム血栓性脳梗塞，肺高血圧症，冠動脈疾患，高血圧症などの発症や予後と関連があり，RNF213関連血管症という新しい疾患概念が提唱されている．

参考文献

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2）Liu W, et al：Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. PLoS One 6：e22542, 2011

3）Kamada F, et al：A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet 56：34-40, 2011

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13）Okazaki S, et al：Effect of the RNF213 p.R4810K variant on the progression of intracranial artery stenosis. Neurol Genet 8：e200029, 2022

14）Hiraide T, et al：Poor outcomes in carriers of the RNF213 variant（p.Arg4810Lys）with pulmonary arterial hypertension. J Heart Lung Transplant 39：103-112, 2020

15）Tabara Y, et al：The association between the moyamoya disease susceptible gene RNF213 variant and incident cardiovascular disease in a general population；The Nagahama study. J Hypertens 39：2521-2526, 2021

16）Koizumi A, et al：P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure. Environ Health Prev Med 18：121-129, 2013

17）Choi EH, et al：Ring finger protein 213 variant and plaque characteristics, vascular remodeling, and hemodynamics in patients with intracranial atherosclerotic stroke；A high-resolution magnetic resonance imaging and hemodynamic study. J Am Heart Assoc 8：e011996, 2019

18）Yamaguchi E, et al：Association of the RNF213 p.R4810K variant with the outer diameter of cervical arteries in patients with ischemic stroke. Stroke Vasc Interv Neurol 2：e000298, 2022