title: P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure.
abstract: BACKGROUND
  Moyamoya disease-an idiopathic vascular disorder of intracranial arteries-is often accompanied by hypertension. RNF213 has been identified as a susceptibility gene for moyamoya disease. In the present study, the association of p.R4810K (G>A) with blood pressure (BP) was investigated in a Japanese population.
  
  
  RESULTS
  Three independent study populations, the Nyukawa (n = 984), Noshiro (n = 2,443) and Field (n = 881) studies, joined this study. BP, body weight and height were measured. Past and present symptoms and disease and medication histories were assessed by interview. Associations of p.R4810K (rs112735431, ss179362673) of RNF213 with BP were investigated. Two linkage disequilibrium blocks were constructed for moyamoya patients with p.R4810K (n = 140) and the general population (n = 384) using 39 single nucleotide polymorphisms (SNPs) spanning 390 kb around RNF213. A total of 60 carriers (3 for AA genotype and 57 for GA genotype) were found in these samples, and the minor allele frequencies were 1.4 % in the Nyukawa and Field studies and 0.2 % in the Noshiro study. Regression analyses adjusted for age, sex and body mass index based on an additive model demonstrated significant associations with systolic BP (mmHg/allele): β (standard error) was 8.2 (2.9) in the Nyukawa study (P = 4.7 × 10(-3)), 18.7 (5.4) in the Noshiro study (P = 4.6 × 10(-4)) and 8.9 (2.0) (P = 1.0 × 10(-5)) in the three populations. In contrast, diastolic BP showed significant associations only in the Noshiro study. Linkage disequilibrium blocks contained none of the BP-associated proxy SNPs reported by previous studies.
  
  
  CONCLUSIONS
  Our study suggests that p.R4810K of RNF213 is associated strongly with systolic BP.
authors.affiliation: Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. koizumi.akio.5v@kyoto-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
authors.forename: Hatasu
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Wanyang
authors.initials: W
authors.lastname: Liu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujii
authors.forename: S T M L D
authors.initials: ST
authors.lastname: Senevirathna
authors.forename: Shanika
authors.initials: S
authors.lastname: Nanayakkara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okuda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitomi
authors.forename: Kouji H
authors.initials: KH
authors.lastname: Harada
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Takenaka
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shimbo
mesh_terms: D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009072:Moyamoya Disease / Q000453:epidemiology* / Q000235:genetics*; D018529:Nutritional Support; D020641:Polymorphism, Single Nucleotide; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases