P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure

Akio Koizumi, Hatasu Kobayashi, Wanyang Liu, Yukiko Fujii, Lalantha Senevirathna, Shanika Nanayakkara, Hiroko Okuda, Toshiaki Hitomi, Kouji H Harada, Katsunobu Takenaka, Takao Watanabe, Shinichiro Shimbo

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56 Citations (Scopus)



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.

Methodology/principal findings

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.


Our study suggests that p.R4810K of RNF213 is associated strongly with systolic BP.
Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalEnvironmental Health and Preventive Medicine
Issue number2
Early online date10 Aug 2012
Publication statusPublished - 2013


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