Yuki Shinya1, Satoru Miyawaki2, Hideaki Imai3, Hiroki Hongo3, Hideaki Ono3, Atsumi Takenobu4, Hirofumi Nakatomi3, Akira Teraoka4, Nobuhito Saito3. 1. Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Neurosurgery, Teraoka Memorial Hospital, Fukuyama, Hiroshima, Japan. 2. Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: miyawaki-tky@umin.ac.jp. 3. Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. 4. Department of Neurosurgery, Teraoka Memorial Hospital, Fukuyama, Hiroshima, Japan.
Abstract
BACKGROUND: Intracranial atherosclerosis of the anterior circulation (anterior ICAS) and intracranial atherosclerosis of the posterior circulation (posterior ICAS) are thought to involve different pathogeneses and risk factors. Recently, we identified a genetic variant that has a significant association with ICAS. The variant was ring finger protein 213 (RNF213) c.14576G>A (rs112735431), which was originally identified as a susceptibility genetic variant for moyamoya disease (MMD). The present study investigated the association of RNF213 c.14576G>A with anterior and posterior ICAS. MATERIALS AND METHODS: A total of 221 study participants (43 with anterior ICAS, 61 with posterior ICAS, 12 with extracranial carotid atherosclerosis [ECAS], 5 with MMD, and 100 control subjects) were recruited from April 2015 to October 2015. A genetic analysis of RNF213 c.14576G>A and an association study with these cerebrovascular diseases were performed. RESULTS: RNF213 c.14576G>A was present in 10 of 43 patients in the anterior ICAS group and 4 of 5 patients in the MMD group, but was not present in the patients in the posterior ICAS and ECAS groups. c.14576G>A was found in 2 of 100 patients in the control group. RNF213 c.14576G>A showed a significant association with anterior ICAS (allele count: P = 3.9 × 10-5, odds ratio [OR] = 13.0, 95% confidence interval [CI] = 2.8-60.8; prevalence of carriers of c.14576G>A: P = 2.6 × 10-5, OR = 14.8, 95% CI = 3.1-71.3). However, RNF213 c.14576G>A showed no association with posterior ICAS. RNF213 c.14576G>A also had a significant association with MMD and had no association with ECAS. CONCLUSIONS: The genetic variant RNF213 c.14576G>A is significantly associated with anterior ICAS but not with posterior ICAS. The present findings may indicate factors involved in the pathogenesis of ICAS-related stroke.
BACKGROUND:Intracranial atherosclerosis of the anterior circulation (anterior ICAS) and intracranial atherosclerosis of the posterior circulation (posterior ICAS) are thought to involve different pathogeneses and risk factors. Recently, we identified a genetic variant that has a significant association with ICAS. The variant was ring finger protein 213 (RNF213) c.14576G>A (rs112735431), which was originally identified as a susceptibility genetic variant for moyamoya disease (MMD). The present study investigated the association of RNF213 c.14576G>A with anterior and posterior ICAS. MATERIALS AND METHODS: A total of 221 study participants (43 with anterior ICAS, 61 with posterior ICAS, 12 with extracranial carotid atherosclerosis [ECAS], 5 with MMD, and 100 control subjects) were recruited from April 2015 to October 2015. A genetic analysis of RNF213 c.14576G>A and an association study with these cerebrovascular diseases were performed. RESULTS:RNF213 c.14576G>A was present in 10 of 43 patients in the anterior ICAS group and 4 of 5 patients in the MMD group, but was not present in the patients in the posterior ICAS and ECAS groups. c.14576G>A was found in 2 of 100 patients in the control group. RNF213 c.14576G>A showed a significant association with anterior ICAS (allele count: P = 3.9 × 10-5, odds ratio [OR] = 13.0, 95% confidence interval [CI] = 2.8-60.8; prevalence of carriers of c.14576G>A: P = 2.6 × 10-5, OR = 14.8, 95% CI = 3.1-71.3). However, RNF213 c.14576G>A showed no association with posterior ICAS. RNF213 c.14576G>A also had a significant association with MMD and had no association with ECAS. CONCLUSIONS: The genetic variant RNF213 c.14576G>A is significantly associated with anterior ICAS but not with posterior ICAS. The present findings may indicate factors involved in the pathogenesis of ICAS-related stroke.