Rare Variants of RNF213 Are Related to Intracranial Atherosclerosis but Not to Extracranial Atherosclerosis: A Study in a Chinese Community-dwelling Population
Jianxun Fang1, Mingyu Tang1, Xinzhuang Yang1, Fei Han1, Lixin Zhou1, Mingli Li1, Yicheng Zhu1, Ming Yao1, Jun Ni1
1Peking Union Medical College Hospital
Objective:
Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between RNF213 rare variants and ICAS within a Chinese community-dwelling population.
Background:
The relationship between Ring finger protein 213 (RNF213) rare variants and intracranial atherosclerosis (ICAS) remained unelucidated in general Chinese population.
Design/Methods:
The present study included 821 participants from Shunyi cohort. Genetic data of RNF213 rare variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial images were acquired by HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of RNF213 rare variants on vascular imaging characteristics. Stratification by age were conducted with 50 years old set as the cutoff value.
Results:
Ninety-five participants were identified as carriers of RNF213 rare variants. Carotid plaques were observed in 367 (44.7%) participants, while ICAS was identified in 332 (40.4%). Rare variants of RNF213 was not associated with ECAS. Both the presence of rare variants (OR = 2.428, P = 0.024) and numerical count of variants (OR = 2.497, P = 0.015) were significantly associated with ICAS in the group of age ≤50 years. Employing HR-MRI, both variant existence (β = 0.218, P = 0.014) and count (β = 0.255, P = 0.003) were significantly correlated with numerical count of 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.
Conclusions:
Rare Variants of RNF213 is associated with age-related ICAS in general Chinese population, suggesting RNF213 might serve as potential rationales for ethnic difference of ICAS.