Background and purpose: Recently, we reported a common genetic variant, ring finger protein 213 (RNF213) c.14576G>A variant, a susceptibility gene for moyamoya disease (MMD), among patients with intracranial major artery stenosis/occlusion (ICASO) in a selected Japanese population. The aim of this 2-center-based case-control study was to confirm our previous finding in a larger population.
Methods: Study participants were recruited from The University of Tokyo Hospital and Kanto Neurosurgical Hospital. The occurrence rate of c.14576G>A variant was investigated in 323 patients, 22 with definite MMD, 8 with unilateral MMD, 84 with ICASO in the absence of MMD (non-MMD ICASO), 34 with extracranial carotid atherosclerosis, 44 with cerebral aneurysm, 21 with intracerebral hemorrhage, and 110 control subjects.
Results: RNF213 c.14576G>A variant was found in 1.8% (2/110) of the normal control group and had significant associations with definite MMD (P<0.0001; odds ratio, 144.0; 95% confidence interval, 26.7-775.9), unilateral MMD (P=0.0001; odds ratio, 54.0; 95% confidence interval, 7.5-386.8), and non-MMD ICASO (P<0.0001; odds ratio, 16.8; 95% confidence interval, 3.81-74.5). There was no significant association with extracranial carotid atherosclerosis, cerebral aneurysm, or intracerebral hemorrhage. This result replicated our previous findings.
Conclusions: A particular subset of patients with various phenotypes of ICASO has a common genetic variant, RNF213 c.14576G>A, indicating that RNF213 c.14576G>A variant is a high-risk allele for ICASO.
Keywords: RNF213; genetics; intracranial atherosclerosis; moyamoya disease.