Zhang Qian, Liu Yaping, Yu Lebao, Duan Ran, Ma Yonggang, Ge Peicong, Zhang Dong, Zhang Yan, Wang Rong, Wang Shuo, Zhao Yuanli, Cao Yong, Liu Xingju, Deng Xiaofeng, Zhao Jizong, Zhang Xue
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
World Neurosurg. 2017 Mar;99:701-708.e1. doi: 10.1016/j.wneu.2016.12.119. Epub 2017 Jan 5.
Quasi-moyamoya disease (MMD) is characterized by moyamoya vasculopathy and well-recognized comorbidity. Whether the recently identified MMD susceptibility gene variant, p.R4810K (rs112735431), is associated with quasi-MMD remains unclear.
This study was a 2-hospital-based case-control study that was conducted in the neurosurgical departments of Beijing Tiantan Hospital and Peking University International Hospital. A total of 42 patients and 161 controls were enrolled. The p.R4810K polymorphism was assessed with Sanger sequencing. A review of the pertinent literature on the p.R4810K polymorphism and quasi-MMD was performed.
The mean age of patients at diagnosis was 34.9 ± 16.5 years with a one-peak distribution in the forties; 57.1% of the patients were female. The p.R4810K heterozygous variant was identified in 5 patients, including 3 patients with atherosclerosis, 1 patient with Graves disease, and 1 patient with rheumatoid arthritis; it was also observed in one control. The frequencies of the A allele and the G/A genotype of rs112735431 (p.R4810K) were significantly greater in the patients with quasi-MMD than in the control groups (5.95% vs. 0.31%, odds ratio [OR] 20.316, P = 0.002; 11.9% vs. 0.6%, OR 21.622, P = 0.002, respectively). In the subgroup analysis, the rs112735431 G/A genotype was significantly associated with arteriosclerotic or autoimmune quasi-MMD (P = 0.006, OR 25.263, confidence interval 2.501-255.175; P = 0.015, OR 29.091, confidence interval 2.444-346.334, respectively).
The p.R4810K variant was associated with atherosclerotic and autoimmune quasi-MMD in a Chinese population, and a lower prevalence of this variant in patients with quasi-MMD compared with patients with MMD was observed.
类烟雾病（MMD）的特征为烟雾样血管病变及公认的合并症。最近鉴定出的MMD易感基因变异p.R4810K（rs112735431）是否与类MMD相关尚不清楚。
本研究是一项基于两家医院的病例对照研究，在北京天坛医院和北京大学国际医院神经外科开展。共纳入42例患者和161例对照。采用桑格测序法评估p.R4810K多态性。对有关p.R4810K多态性和类MMD的相关文献进行了综述。
患者诊断时的平均年龄为34.9±16.5岁，呈单峰分布，以四十多岁为主；57.1%的患者为女性。在5例患者中鉴定出p.R4810K杂合变异，其中3例患有动脉粥样硬化，1例患有格雷夫斯病，1例患有类风湿关节炎；在1例对照中也观察到该变异。类MMD患者中rs112735431（p.R4810K）的A等位基因频率和G/A基因型频率显著高于对照组（分别为5.95%对0.31%，比值比[OR]20.316，P = 0.002；11.9%对0.6%，OR 21.622，P = 0.002）。在亚组分析中，rs112735431 G/A基因型与动脉粥样硬化性或自身免疫性类MMD显著相关（分别为P = 0.006，OR 25.263，置信区间2.501 - 255.175；P = 0.015，OR 29.091，置信区间2.444 - 346.334）。
在中国人群中，p.R4810K变异与动脉粥样硬化性和自身免疫性类MMD相关，且观察到类MMD患者中该变异的患病率低于MMD患者。
