Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Center for bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
J Stroke Cerebrovasc Dis. 2024 Nov;33(11):107982. doi: 10.1016/j.jstrokecerebrovasdis.2024.107982. Epub 2024 Sep 2.
The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population.
The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value.
Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (β = 0.150, P = 0.025) and numerical count of variants (β = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (β = 0.154, P = 0.014) and variant count (β = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors.
Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.
环指蛋白 213（RNF213）中的罕见变异与颅内动脉粥样硬化（ICAS）之间的关系仍不清楚。本研究使用全外显子组测序（WES）和高分辨率磁共振成像（HR-MRI），旨在调查中国社区人群中罕见 RNF213 变异与 ICAS 之间的关联。
本研究纳入了来自顺义队列的 821 名参与者。通过 WES 获得罕见 RNF213 变异的遗传数据，并按功能域进行分类。通过脑 HR-MRI 和颈动脉超声分别评估颅内和颅外动脉粥样硬化。使用逻辑回归和广义线性回归评估罕见 RNF213 变异对动脉粥样硬化的影响。以 50 岁为截止值进行年龄分层。
95 名参与者被确定为携带罕见 RNF213 变异。367 名（44.7%）参与者存在颈动脉斑块，306 名（37.3%）参与者存在 ICAS。RNF213 的罕见变异与 ECAS 无关。采用 HR-MRI，在年龄≤50 岁的组中，罕见变异的存在（β=0.150，P=0.025）和变异数（β=0.182，P=0.003）与 ICAS 显著相关。变异的存在（β=0.154，P=0.014）和变异数（β=0.188，P=0.003）与年轻亚组大脑中动脉的斑块也显著相关，而不是基底动脉。此外，在年轻亚组中，位于 N 臂域外的变异与 ICAS 之间存在显著关联（OR=2.522，P=0.030）。在调整年龄、性别和心血管危险因素后，统计结果仍然稳健。
RNF213 的罕见变异与一般中国人群中与年龄相关的 ICAS 相关，突出了 RNF213 作为早发性 ICAS 遗传贡献者的潜在作用。
