Intracranial Vessel Morphology in RNF213-Related Vasculopathy: A Quantitative Imaging Study in Ischemic Stroke Patients

Background and Purpose The RNF213 p.R4810K variant is a major susceptibility allele for moyamoya disease (MMD) in East Asians. This study investigated the relationship between RNF213 variants and intracranial vessel morphology in acute ischemic stroke.Methods Patients from the Samsung Medical Center (SMC) Stroke Registry (2017–2019) were included. Quantitative vessel features were extracted from magnetic resonance angiography, including the basal global tortuosity index (GTIb), internal carotid artery (ICA) area, and basal minimum-to-maximum diameter ratio (MMRb). Genome-wide association analyses of GTIb, ICA area, and MMRb were performed (n=945). Validation was conducted in an independent Korea University Medical Center (KUMC) cohort. Groupwise comparisons were performed across three predefined groups: MMD+/variant+, MMD-/variant+, and MMD-/variant-. Adjusted linear regressions for ICA area were performed. Receiver operating characteristic (ROC) analyses evaluated GTIb, ICA area, and a combined model for identifying RNF213 carriers.Results GTIb and ICA area showed genome-wide significance at the RNF213 locus (p.R4810K), whereas MMRb did not. In the KUMC cohort, ICA area differed between variant+ and variant-groups, while GTIb and MMRb did not. Across SMC groups (MMD+/variant+ [n=14], MMD-/variant+ [n=37], MMD-/variant- [n=888]), GTIb was highest and ICA area and MMRb smallest in MMD+/variant+, intermediate in MMD-/variant+, and lowest/largest in MMD-/variant- (P<0.001). ICA area differences remained significant after multivariable adjustment. In ROC analyses, ICA area provided significant incremental discrimination beyond clinical variables.Conclusions The RNF213 variant was consistently associated with smaller ICA area in patients with ischemic stroke. The association with intracranial tortuosity was not reproduced in the validation cohort.