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

Year: 2026

Type: article

Abstract: 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.

Source: Journal of Stroke

DOI: 10.5853/jos.2025.06282