RESUMEN
Moyamoya disease (MMD) is a chronic progressive steno-occlusive vasculopathy that involves terminal portions of the bilateral internal carotid arteries and/or the initial segment of the middle cerebral arteries and/or the initial segment of the anterior cerebral arteries. Ring finger protein 213 gene (RNF213) is considered as the major susceptibility gene of MMD.RNF213p.R4810K is mainly distributed in East Asians and is the founder variant of Asian patients with MMD.RNF213p.R4810K is associated with the incidence, prevalence, severity of illness and clinical manifestations of MMD. The biochemical mechanisms ofRNF213p.R4810K are still unclear and may affect angiogenesis of endothelial cells through both cell cycle-dependent and cell cycle-independent mechanisms. This paper reviews the research progress ofRNF213p.R4810K and the related mechanisms in MMD.
RESUMEN
BACKGROUND AND PURPOSE: The ring finger protein 213 (RNF213) gene R4810K variant, a susceptibility locus for moyamoya disease (MMD), has recently been identified to be associated with intracranial major artery stenosis/occlusion (ICASO) without satisfying the diagnostic criteria of MMD in the Japanese population. However, further studies are needed to determine whether this variant is associated with ICASO in other populations and whether R4810K variant-related ICASO could be categorized as MMD. The aim of this study is to elucidate whether the R4810K variant was associated with ICASO among the Han Chinese population and potential histopathology of R4810K variant-related ICASO. MATERIALS AND METHODS: We conducted a case-control study to evaluate association and performed high-resolution (HR) magnetic resonance imaging (MRI) to investigate arterial wall feature of ICASO. The R4810K variant was genotyped in 114 ICASO patients and 268 controls. Then, patients with R4810K variant-related ICASO were subjected to HR MRI examination and presumptively diagnosed based on the characteristics thus observed. STATISTICAL ANALYSIS: The relationship between R4810K variant and ICASO was evaluated by Fisher's exact test with odds ratios (OR) and 95% confidence interval (CI). RESULTS: The R4810K variant was associated with ICASO and increased the risk for ICASO (P < 0.01; OR: 20.2; 95% CI: 2.5-163.11). Presumptive MMD was diagnosed in all female patients with R4810K variant. However, presumptive intracranial atherosclerotic stenosis was diagnosed in one of three males harboring this variant. CONCLUSIONS: The R4810K variant is a genetic risk factor for ICASO among the Han Chinese population and that R4810K variant-related ICASO should be identified as MMD in female but not uncertain in male patients.