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 × 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 × 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.

ObjectiveMoyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology, sharing many similar clinical symptoms with other vascular disorders. This study aimed to investigate gene dysregulation in peripheral blood of MMD and compare it with other vascular disorders.MethodsTranscriptomic profiles of 12 MMD patients and 8 healthy controls were obtained using RNA sequencing. Differentially expressed genes (DEGs) were identified and several were validated by quantitative real-time PCR in independent samples. Biological pathway enrichment analysis of DEGs and deconvolution of leukocyte subsets in peripheral blood were performed. Expression profiles for other vascular diseases were downloaded from public database and consistent DEGs were calculated. Gene set enrichment analysis (GSEA) was conducted to compare gene dysregulation pattern between MMD and other vascular diseases.ResultsA total of 533 DEGs were identified for MMD. Up-regulated genes were mainly involved in extracellular matrix (ECM) organization, whereas down-regulated genes were primarily associated with inflammatory and immune responses. As for cell populations, significantly increased naïve B cells and naïve CD4 cells as well as obviously decreased resting natural killer cells were observed in peripheral blood of MMD patients. GSEA analysis indicated that only up-regulated genes of ischemic stroke and down-regulated genes of coronary artery disease and myocardial infarction were enriched in up-regulated and down-regulated genes of MMD, respectively.ConclusionDysregulated genes in peripheral blood of MMD mainly played key roles in ECM organization, inflammatory and immune responses. This gene dysregulation pattern was specific compared with other vascular diseases. Besides, naïve B cells, naïve CD4 cells and resting natural killer cells were aberrantly disrupted in peripheral blood of MMD patients. These results will help elucidate the complicated pathogenic mechanism of MMD.

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OBJECTIVE This prospective study was designed to confirm the role of atorvastatin in collateral circulation formation induced by encephaloduroarteriosynangiosis (EDAS) in patients with moyamoya disease (MMD). METHODS Patients who were diagnosed with MMD at the Department of Neurosurgery in the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China, between June 2017 and May 2018 were included. Blood samples were obtained from an antecubital vein and were analyzed using flow cytometry. Endothelial progenitor cells (EPCs) were defined as CD34brCD133+CD45dimKDR+. All patients included in the study underwent EDAS. Patients voluntarily chose whether to undergo atorvastatin treatment after EDAS. The correlation between atorvastatin and good postoperative collateral circulation was evaluated. RESULTS A total of 106 patients with MMD were included in this study. Fifty-three patients (50%) received atorvastatin treatment. The baseline characteristics did not display statistically significant differences between the atorvastatin-treated and non-atorvastatin groups. Seventy-eight (42.9%) of the 182 hemispheres investigated postoperatively were classified as grade A collateral circulation, 47 (25.8%) as grade B, and 57 (31.3%) as grade C. Multivariate analysis revealed that only atorvastatin was significantly correlated with good collateral circulation after EDAS (p = 0.041). CONCLUSIONS The results of this prospective clinical trial have indicated that atorvastatin administered at 20 mg daily is safe and effective for the formation of postoperative collateral induced by EDAS.