Ring Finger Protein 213 Variant and Plaque Characteristics, Vascular Remodeling, and Hemodynamics in Patients With Intracranial Atherosclerotic Stroke: A High‐Resolution Magnetic Resonance Imaging and Hemodynamic Study

Background Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized that patients with the ring finger protein 213 (RNF213) variant, a susceptibility locus for moyamoya disease in Asians, have different neuroimaging characteristics in terms of the vessel wall and hemodynamics. Methods and Results We analyzed consecutive patients with ischemic events in middle cerebral artery distribution and relevant plaques of the distal internal carotid artery or proximal middle cerebral artery on high‐resolution magnetic resonance imaging. Patients with carotid/cardiac sources of embolism or moyamoya disease were excluded. High‐resolution magnetic resonance imaging features (eg, outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time‐of‐flight magnetic resonance angiography) were compared between RNF213 p.Arg4810Lys variant carriers and noncarriers. Among 144 patients included, 44 (29.9%) had the RNF213 variant. Clinical characteristics, including age, sex, body mass index, and vascular risk factors, were not significantly different between RNF213 variant carriers and noncarriers. However, the outer vessel diameter was smaller in RNF213 variant carriers than in noncarriers (P<0.0001 for middle cerebral artery of relevant stenosis [2.05‐mm analysis of RNF213 gene for moyamoya disease in the Chinese HAN population 2.75 mm]; P<0.0001 for contralateral side [2.42 versus 3.00 mm] and P<0.001 for basilar artery [3.19 versus 3.53 mm]). Other high‐resolution magnetic resonance imaging features, including plaque morphology and eccentricity, were not significantly different. Fractional flow was diminished in patients with smaller‐diameter intracranial arteries with a similar degree of stenosis. Conclusions The RNF213 variant may be associated with vasculogenesis, but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. In addition to antiatherosclerotic strategies, further studies are warranted to develop novel therapeutic strategies against RNF213 vasculopathy in Asians.