Abstract WP271: The Role of Ring Finger Protein213 Variant in Patients With Intracranial Atherosclerotic Disease

Abstract

Introduction: The Ring Finger Protein213 ( RNF213 ) gene variant is a relatively common variant in general population of East Asian countries (0.43 to 1.8%). Recently, RNF213 is reportedly a susceptibility gene not only for moyamoya disease (MMD) but also for intracranial atherosclerosis (ICAS) in this population. However, the role of this genetic factor in patients with ICAS is unknown. We hypothesized that this variant is involved in the pathogenesis of ICAS. Methods: We conducted a prospective study of patients with ICAS and MMD using high-resolution MRI (HR-MRI) and RNF213 (p.Arg4810Lys variant) gene studies. Patients were classified into intracranial atherosclerosis (ICAS) when relevant plaques existed on HR-MRI and moyamoya disease (MMD) when patients had RNF213 variant and HR-MRI showed no plaque but characteristic features of MMD (negative remodeling and basal collaterals). We compared clinical and neuroimaging features between (a) the RNF213 - ICAS, (b) the RNF213 + ICAS, and (c) MMD group. Results: Among 178 patients analyzed, 79 were the RNF213 - ICAS, 37 the RNF213 variant+ ICAS, and 62 the MMD group. Vascular risk factors were more frequently observed in ICAS than MMD patients, but there was no difference between RNF213 - ICAS and the RNF213 variant+ ICAS. Moreover, the site of occlusive disease was different between ICAS and MMD patients, but not between RNF213 - ICAS and the RNF213 variant+ ICAS. It was more distally located in RNF213 variant+ ICAS than in MMD (p=0.012). Compared to RNF213 - ICAS patients, tandem lesions were significantly more common in RNF213 + ICAS (24.1% vs. 67.6%, p<0.05), after adjusted for vascular risk factors. Conclusions: Patients with ICAS and the RNF213 variant showed distinct clinical and imaging features from MMD patients. A high frequency of tandem lesions in RNF213 + ICAS suggest that this variant may have synergic effects in atherosclerosis which should be tested in a larger cohort.