Rare RNF213 variants is related to early-onset intracranial atherosclerosis: A Chinese community-based study

Area of Science:

• Genetics
• Neurology
• Cardiovascular Disease

Background:

• The association between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) was previously unclear.
• Understanding this relationship is crucial for identifying genetic predispositions to cerebrovascular diseases.

Purpose of the Study:

• To investigate the association between rare RNF213 variants and ICAS in a Chinese community-dwelling population.
• To explore the role of RNF213 in the pathogenesis of early-onset ICAS.

Main Methods:

• Whole-exome sequencing (WES) was used to identify rare RNF213 variants in 821 participants.
• High-resolution magnetic resonance imaging (HR-MRI) assessed intracranial atherosclerosis.
• Logistic and generalized linear regression analyses were performed, with age stratification at 50 years.

Main Results:

• Rare RNF213 variants showed a significant correlation with ICAS in individuals aged 50 years or younger (P = 0.025).
• Variant presence and count were associated with middle cerebral artery plaques in the younger subgroup.
• Variants outside the N-arm domain were significantly linked to ICAS in younger participants (OR = 2.522, P = 0.030).

Conclusions:

• Rare RNF213 variants are associated with age-related ICAS in the Chinese population.
• RNF213 may play a role as a genetic contributor to early-onset ICAS.
• These findings highlight RNF213 as a potential target for understanding and managing ICAS.