Smaller outer diameter of atherosclerotic middle cerebral artery associated with RNF213 c.14576G>A Variant (rs112735431)

BACKGROUND Intracranial atherosclerosis (ICAS) involves diverse histologies and several remodeling patterns. Ring finger protein 213 (RNF213) c.14576G>A variant (rs112735431), recently reported to be associated with ICAS, may be linked with negative remodeling (outer diameter - reducing morphological alteration) of intracranial arteries. This study investigated the outer diameter of atherosclerotic middle cerebral artery (MCA). METHODS Patients with unilateral atherosclerotic MCA stenosis/occlusion were enrolled in this single-hospital-based case-control study at The University of Tokyo Hospital. The patients were divided into two groups by the presence of RNF213 c.14576G>A (variant group and wild-type group) and the outer diameter of the MCA was measured with high-resolution magnetic resonance imaging. RESULTS Twenty-eight patients with the wild type and 19 patients with the variant type were included. The outer diameter of the stenotic side MCA was smaller in the variant group than in the wild-type group (P = 8.3 × 10-6). The outer diameter of the normal side MCA was also smaller in the variant group than in the wild-type group (P = 5.2 × 10-3). The ratio of stenotic side to normal side was also smaller in the variant group than in the wild-type group (P = 1.5 × 10-5). CONCLUSIONS This study indicates that RNF213 c.14576G>A is associated with negative remodeling of ICAS.