Distinct impact of RNF213 p.R4810K genotype on transdural collateral formation across Japanese Asian and Polish...

Interethnic differences in natural transdural collaterals-an angiographical hallmark of Moyamoya disease (MMD)-may reflect the genetic and pathophysiological mechanisms underlying ethnic disparities. However, international comparative studies incorporating both angiographic and genetic data are limited. This study investigated differences in cerebral angioarchitecture and clinical presentation between Japanese Asian and Polish Caucasian patients with MMD, with a focus on the RNF213 p.R4810K variant, a known East Asian founder mutation. We retrospectively analyzed consecutive 94 Japanese and 33 Polish patients who underwent diagnostic cerebral angiography and RNF213 p.R4810K genotyping between 2015 and 2025. Suzuki's angiographical stages and the presence of natural-transdural, periventricular, and leptomeningeal collaterals, mainly via posterior cerebral artery (PCA), were evaluated. Interethnic comparisons progressed from full cohort comparisons to genotype-based subgroup analyses with adjustments for angiographical stage and RNF213 p.R4810K genotype. The RNF213 p.R4810K wild-type was present in 31% of Japanese and 100% of Polish patients. A trend toward more hemorrhagic presentation in Japanese was noted (17% vs. 12%, P = 0.10). Polish patients were significantly younger at diagnosis (P = 0.0014). Among 230 un-operated hemispheres, angiographic stages did not significantly differ (P = 0.23). After adjustment, overall prevalence of natural transdural collaterals was similar (41% in entire Japanese and 60% in Polish cohort, P = 0.20), but significantly higher in Polish than in Japanese patients with the wild-type genotype (60% vs 34%, P = 0.0098). Periventricular collaterals were significantly more common in Japanese, independent of genotype (P < 0.0001). No interethnic difference was observed in leptomeningeal collaterals. In conclusion, Polish MMD patients exhibit more natural transdural and fewer periventricular collaterals than Japanese with the wild-type genotype. These genetic and ethnic differences suggest distinct mechanisms of collateral formation across ethnic groups, with implications for genotype-driven pathophysiology and clinical presentation in MMD.