Genetic Variant RNF213 c.14576G>A in Various Phenotypes of Intracranial Major Artery Stenosis/Occlusion
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.
- Received June 28, 2013.
- Accepted July 8, 2013.
- © 2013 American Heart Association, Inc.