Genetic analysis of intracranial major artery stenosis: Analysis of moyamoya disease associated gene RNF213

Abstract

Intracranial major artery stenosis/occlusion (ICASO) is one of the most common causes of stroke. The most common cause of ICASO is atherosclerosis, caused by acquired factors, such as hypertension, diabetes mellitus, dyslipidemia, and smoking. However, ICASO is known to be common among nonwhite populations, particularly Asian populations, indicating a potential involvement of genetic factors. Recently, a susceptibility gene for moyamoya disease (MMD), ring finger protein 213 (RNF213) was identified in the East Asian population. We have reported that the same genetic variant (nonsynonymous mutation), c.14576G>A (p.R4859K) variant, in RNF213 has significant association with various phenotypes of ICASO. This identification of a common genetic variant among ICASO lesions may lead to a new genetic diagnosis system in the field of stroke, conventionally thought to be caused by acquired risk factors. Preventive treatment for stroke, such as blood pressure management, and image screening, such as MR angiography, for intracranial cerebral arterial lesion would be very important, especially for individuals with this specific allele, which is present in ≈2% of the Japanese population