Prevalence of RNF213 variants in symptomatic intracranial arterial stenosis/occlusion in China

• Published in: Molecular genetics and genomics : MGG 2020-05, Vol.295 (3), p.635-643
• Main Authors: Sun, Xunsha, Luo, Man, Li, Jiaoxing, Lai, Rong, Lin, Jing, Wang, Yufang, Xu, Xiaowei, Wu, Shaoqing, Sheng, Wenli
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Aged; Animal Genetics and Genomics; Arteriosclerosis; Asian Continental Ancestry Group - genetics; Biochemistry; Biomedical and Life Sciences; Case-Control Studies; China - epidemiology; Constriction, Pathologic - epidemiology; Constriction, Pathologic - genetics; Constriction, Pathologic - pathology; Female; Genetic Predisposition to Disease; Hemorrhage; Human Genetics; Humans; Ischemia; Life Sciences; Male; Meta-Analysis as Topic; Microbial Genetics and Genomics; Middle Aged; Moyamoya Disease - epidemiology; Moyamoya Disease - genetics; Moyamoya Disease - pathology; Occlusion; Original Article; Plant Genetics and Genomics; Polymorphism, Single Nucleotide; Prevalence; Risk factors; Stenosis; Stroke; Ubiquitin-Protein Ligases - genetics; Veins & arteries
• ISSN: 1617-4615; 1617-4623
• DOI: 10.1007/s00438-020-01650-4

The ring finger protein 213 gene ( RNF213 ) rs112735431 was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. We conducted a case–control study to examine the prevalence and correlates of the RNF213 rare variants in Chinese patients with symptomatic ICASO. A total of 503 cases including 390 ischemic stroke patients (ICASO-IS), 113 intracranial hemorrhage patients (ICASO-ICH) and 227 control subjects were recruited. The snapshot technique was used for RNF213 rare variants analysis, including rs112735431, rs148731719, rs37144111 and rs138130613. Moreover, a meta-analysis was performed to explore the relationship between RNF213 variants and ICASO in Asian. In our case–control study, we found that the rs138130613 variant was significantly associated with ICASO-IS (OR = 9.92, 95% CI 1.24–79.19, p  = 0.03). The mean age of first ischemic stroke onset of variant carriers was earlier than the noncarriers (51.3 ± 18.0 versus 66.0 ± 12.9 years old, p  = 0.02), but the conventional atherosclerotic risk factors and the characteristics of artery stenosis did not differ between them. In addition, the meta-analysis showed significant association between the rs112735431 polymorphism and the ICASO or ICASO-IS, and this variant was found more often in women and young-onset patients in Asia. This study suggests that the RNF213 rs112735431 and rs138130613 are genetic risk variants for ischemic stroke with intracranial artery stenosis/occlusion in China and rs112735431 is also associated with the high risk of ICASO in Asia. Further large-scale investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of symptomatic ICASO.