Meta‐Analysis of Genotype and Phenotype Studies Confirms Predictive Roles of the RNF213 p.R4810K for Moyamoya Disease

BACKGROUND AND PURPOSE The aim of this meta-analysis study was to assess the predictive effects of RNF213 p.R4810K on phenotype in MMD. METHODS Electronic databases (Pubmed, EMBASE, etc) were searched and the relevant articles (published till August 2020) were retrieved. Review Manage 5.3 and Stata 12.0 were applied to complete all statistical analyses. Pooled odds ratios (ORs), 95% confidence intervals (CIs), and three comparison models were evaluated to analyze the association using a fixed-effect model. RESULTS A total of 2798 patients with MMD were selected and the effects of heterozygous or homozygous RNF213 p.R4810K on 18 clinical features were identified. The patients of under 15 years were more common in GA and AA groups (AA vs GA: P = 0.009; AA vs GG: P = 0.003; GA vs GG: P = 0.001). Of homozygotes, the most affected MMD before age 4 (AA vs GA: P < 0.00001; AA vs GG: P < 0.00001). The frequency of infarctions and transient ischemic attack was significantly higher in homozygotes or heterozygotes. However, the frequency of intracerebral/intraventricular hemorrhage was lower in patients with the GA than GG genotype. More patients with MMD having a family history of the disease with AA and GA genotypes (P = 0.003, P < 0.00001, respectively). Posterior cerebral artery involvement was more common in GA patients (P < 0.00001). CONCLUSION The homozygous or heterozygous RNF213 may be an efficient biomarker to classify different clinical phenotypes of MMD.