Introduction: Ring finger protein 213 (RNF213) gene R4810K variant,a susceptibility locus for moyamoya disease disease (MMD) in eastern Asian, has also recently been identified as a susceptibility locus for non-MMD Intracranial Major Artery Stenosis/Occlusion (non-MMD ICASO). Due to genetic heterogeneity, further studies are needed to verify whether the R4810K variant of RNF213 is associated with ICASO in other populations.
Methods: RNF213 gene R4810K variant was genotyped in 114 patients with non-MMD ICASO (male, 78.9%) and 268 healthy controls(male, 73.5%)from the Chinese Han population. Association between RNF213 gene R4810K variant and non-MMD ICASO was analyzed in a case-control study. Patients with RNF213 variant-related ICASO were scanned High resolution (HR)-MRI, and the presumptive diagnosis of these patients was made based on the HR-MRI characteristics.
Results: The RNF213 R4810K variant was observed in 8 (7.0%, including 5 females) patients with non-MMD ICASO and only in 1 (0.4%) healthy control. The RNF213 R4810K variant was associated with non-MMD ICASO and increased the risk for non-MMD ICASO (P<0.01; OR, 20.2; 95% confidence interval, 2.5-163.1) (Figure 1A). Presumptive MMD based on HR-MRI findings was diagnosed in all female patients with RNF213 variant-related ICASO. However, presumptive intracranial atherosclerotic stenosis was diagnosed based on HR-MRI findings in one of three males harboring the RNF213 variant (Figure 1B).
Conclusions: RNF213 R4810K appears to be a genetic risk variant for non-MMD ICASO among the Chinese Han population. HR-MRI supported that RNF213 variant-related ICASO should be identified as MMD in female patients. However, a similar relationship could not be established among male patients. Our data suggest that detection of R4810K in female patients with ICASO is a useful biomarker to differentiate MMD from other ICASO.