title: A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis.
abstract: BACKGROUND
  Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque).
  
  
  METHODS
  We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients.
  
  
  RESULTS
  Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944-0.99).
  
  
  CONCLUSIONS
  RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Chung
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Cha
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Je Young
authors.initials: JY
authors.lastname: Yeon
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Pyoung
authors.initials: P
authors.lastname: Jeon
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Chyul
authors.initials: SC
authors.lastname: Hong
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases