Background: Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that Ring Finger 213 (RNF213 p.Arg4810Lys) polymorphism, a susceptibility locus for MMD in East Asian, is a susceptible gene for ICAS confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque).
Method: We analyzed 532 consecutive patients with ischemic events within the MCA distribution and relevant stenotic lesion on distal ICA or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed in 370 (69.5%) patients, and HR-MRI in 283 (53.2%).
Results: Based on angiographic and HR-MRI findings, 234 patients were diagnosed as ICAS, and 288 as MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients as well as 119 (69.1%) MMD patients. The RNF213 variant was observed in 25.2% (33 of 131) of patients with HR-MRI confirmed ICAS. Similarly, 15.8% (6 of 38) of ICAS patients in whom MMD was excluded by angiography had this variant. Among ICAS patients, RNF213 variant carriers were younger and more likely to have family history of MMD than non-carrier. Multivariate testing showed that age of ICAS onset was independent associated with RNF213 variant (odds ratio, 0.97; 95% CI, 0.944-0.99). Other clinical characteristics including vascular risk factors and HR-MRI findings were not different between them.
Conclusions: RNF213 is susceptible gene not only for MMD but also for ICAS in East Asians. Further studies are needed on non-p.Arg4810Lys RNF213 variants in ICAS patients outside East Asian populations.