Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms.

Jinkwon Kim,Min-Hee Woo,Chang Soo Ryu,Young Seok Park,Jung Oh Kim,Nam Keun Kim,Ok Joon Kim,Han Sung Park,Hui Jeong An

doi:10.3390/ijms21061956

Abstract

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke. Recent studies have suggested that variants of RNF213, a susceptibility gene for moyamoya disease (MMD), are also related to non-MMD ICASO. Regarding the predominant involvement of steno-occlusion on anterior circulation in MMD, we hypothesized that the ICASO distribution pattern (anterior/posterior) in non-MMD may differ according to RNF213 variants. This study analyzed 1024 consecutive Korean subjects without MMD who underwent computed tomography angiography (CTA) or magnetic resonance angiography (MRA). We evaluated four single nucleotide polymorphisms (SNPs) in the exon region of RNF213: 4448G > A (rs148731719), 4810G > A (rs112735431), 4863G > A (rs760732823), and 4950G > A (rs371441113). Associations between RNF213 variants and anterior/posterior ICASO were examined using multivariate logistic regression analysis. Anterior ICASO was present in 23.0% of study subjects, and posterior ICASO was present in 8.2%. The GA genotype of RNF213 4810G > A (adjusted odds ratio (AOR) [95% confidence interval (CI)], 2.39 [1.14–4.87] compared to GG; p = 0.018) and GA genotype of RNF213 4950G > A (AOR [95% CI], 1.71 [1.11–2.63] compared to GG; p = 0.015) were more frequent in subjects with anterior ICASO. The genotype frequency of RNF213 4863G > A differed significantly according to the presence of posterior ICASO. Further investigations of the functional and biological roles of RNF213 will improve our understanding of the pathomechanisms of ICASO and cerebrovascular disease.

Highlights

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke [1,2]
This study included 1024 non-moyamoya disease (MMD) subjects (636 ischemic stroke and 388 non-stroke subjects) who underwent genotyping of RNF213 variants and angiographic evaluation
When we evaluated the relationship between RNF213 variants and the distribution of ICASO using the multivariate logistic regressions (Table 4), anterior ICASO was significantly associated with the RNF213 4810 GA genotype (AOR [95% confidence intervals (CI)], 2.39 [1.14–4.87]; p = 0.018) compared with the GG genotype

Summary

Introduction

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke [1,2]. ICASO can be present in anterior and posterior cerebral circulation. It has been known that anterior and posterior ICASO differs in clinical characteristics, risk factors, histopathology, and genetic susceptibility [11,12,13]. RNF213 is recognized as the major susceptibility gene for MMD, which is typically characterized by progressive steno-occlusive changes in the terminal part of the internal carotid arteries and/or their branches (anterior circulation) [14,15]. Regarding the potential genetic contributions to ICASO, we hypothesized that the distribution of anterior/posterior ICASO in non-MMD may differ according to genetic variants of RNF213. We assessed the association between four single nucleotide polymorphisms (SNPs) in the exon region of RNF213 (4448G > A, 4810G > A, 4863G > A, and 4950G > A) and the distribution pattern of ICASO in non-MMD Koreans

Methods

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Discussion

Conclusion