Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease
Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease
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DOI：
10.1212/wnl.0000000000008901
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发表时间：
2020-02-18
期刊：
影响因子：
9.9
通讯作者：
Duan, Lian
中科院分区：
文献类型：
--
作者：
Wang, Yue;Zhang, Zhengshan;Duan, Lian
目的对中国人烟雾病(Moyamoya disease，MMD)患者的一种特殊临床表型进行RNF213基因的精确遗传分析，以确定RNF213基因的杂合性是否与该病的早发和重症有关。方法采用病例对照研究，研究对象为1385名中国MMD患者和2903名正常对照。结果RNF213p.R4810K携带率从东北沿海城市、东北沿海城市、东部沿海城市和内陆地区，RNF213p.R4810K携带率逐渐下降。与对照组相比，MMD患者中p.R4810K的频率更高(优势比为48.1；95%可信区间为29.1-79.6；p=1.6×10(-141))。此外，所有GA和AA基因携带者的发病年龄均低于GG基因携带者，GG、GA和AA基因携带者的中位发病年龄分别为40.0岁、36.0岁和11.5岁，从而证实了GA和AA基因携带者可在生命早期获得MMD。携带GA基因的MMD患者较GG基因携带者更易发生大脑后动脉受累(38.4%vs23.3%，p=8.3×10(-7))。结论RNF213p、R4810K基因携带率与中国MMD发病风险密切相关，且发病年龄较早，PCa受累程度较重。
ObjectivePrecise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.MethodsA case-control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.ResultsAn obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1-79.6; p = 1.6 x 10(-141)). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 x 10(-7)).ConclusionsStrong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.