Identification of RNF213 as a Susceptibility Gene for Moyamoya Disease and Its Possible Role in Vascular Development

もやもや病感受性遺伝子の特定とその機能についての発見. 京都大学プレスリリース. 2011-7-21.Background Moyamoya disease is an idiopathic vascular disorder of intracranial arteries. Its susceptibility locus has been mapped to 17q25.3 in Japanese families, but the susceptibility gene is unknown. Methodology/Principal Findings Genome-wide linkage analysis in eight three-generation families with moyamoya disease revealed linkage to 17q25.3 (P<10-4). Fine mapping demonstrated a 1.5-Mb disease locus bounded by D17S1806 and rs2280147. We conducted exome analysis of the eight index cases in these families, with results filtered through Ng criteria. There was a variant of p.N321S in PCMTD1 and p.R4810K in RNF213 in the 1.5-Mb locus of the eight index cases. The p.N321S variant in PCMTD1 could not be confirmed by the Sanger method. Sequencing RNF213 in 42 index cases confirmed p.R4810K and revealed it to be the only unregistered variant. Genotyping 39 SNPs around RNF213 revealed a founder haplotype transmitted in 42 families. Sequencing the 260-kb region covering the founder haplotype in one index case did not show any coding variants except p.R4810K. A case-control study demonstrated strong association of p.R4810K with moyamoya disease in East Asian populations (251 cases and 707 controls) with an odds ratio of 111.8 (P = 10−119). Sequencing of RNF213 in East Asian cases revealed additional novel variants: p.D4863N, p.E4950D, p.A5021V, p.D5160E, and p.E5176G. Among Caucasian cases, variants p.N3962D, p.D4013N, p.R4062Q and p.P4608S were identified. RNF213 encodes a 591-kDa cytosolic protein that possesses two functional domains: a Walker motif and a RING finger domain. These exhibit ATPase and ubiquitin ligase activities. Although the mutant alleles (p.R4810K or p.D4013N in the RING domain) did not affect transcription levels or ubiquitination activity, knockdown of RNF213 in zebrafish caused irregular wall formation in trunk arteries and abnormal sprouting vessels. Conclusions/Significance We provide evidence suggesting, for the first time, the involvement of RNF213 in genetic susceptibility to moyamoya disease

Association of IL-4 with pachychoroid neovasculopathy

Abstract The purpose of this study was to identify the inflammatory cytokines that were associated with pachychoroid neovasculopathy (PNV). Seventy-five eyes of 75 patients with PNV, 145 eyes of 145 patients with neovascular age-related macular degeneration without pachyvessels, and 150 eyes of 150 normal subjects were examined for the levels of intraocular cytokines. In eyes with PNV, the levels of IL-1α, IL-1β, IL-2, IL-4, IL-10, and VEGF were significantly higher than that of the controls. Logistic regression analysis showed that the highest association with the pachyvessels was found for IL-4, IL-2, and IL-1α. In eyes with PNV, the levels of IL-4, IL-2, IL-5, IL-13, IL-1α, and IL-1β were significantly higher in eyes with both increased choroidal thickness and choroidal vessel diameter. The strongest correlation with the choroidal thickness and vessel diameter was observed for IL-4. In PNV eyes with polypoidal lesions, the levels of IL-4, IL-17, and TNFβ were significantly correlated with the number of polypoidal lesions. Of these cytokines, IL-4 was especially associated with the thickness of the choroidal vessels and the formation of polypoidal lesions. We conclude that IL-4 is most likely involved in establishing the clinical characteristics of PNV and polypoidal vascular remodeling

一人暮らし学生のセルフメディケーションのための準備状況

雑誌掲載版2009年度に一人暮らし新入生の体温計等の医療器具、バンソウコウ等の医療用消耗品、一般用医薬品(OTC)の準備状況を調査した。次年度以降入学予定者には入学前に、セルフメディケーションのために必要な物品を具体的に例示した文書を配布した。その効果と入学後の教育の効果を調査した。対象は2009、10、11年度に栄養、看護、社会福祉学科に入学した学生のうち、保護者もとを離れ一人暮らしをしている者とした。それぞれ、1年次に性別等の属性、医療器具、医療用消耗品、OTCを何品目用意しているかについて質問した。2011年度には、1、2、3年次を対象にOTCに関する知識と、使用状況について質問した。新入生に対する調査では、59.5%から回答を得た。用意していた医療器具、医療用消耗品、OTCの品目数は看護学科の学生がいずれも有意に多かった。また、2009年度入学生に比べ、2010、11年度入学生はOTCの品目数が有意に多かった。2011年度のOTCについての調査では69.0%から回答を得た。2009、10、11年度入学生は、それぞれ3、2、1年生となっているが、薬理学履修学生はOTCに関する知識が有意に高かった。しかし、使用や保管に関する注意事項の遵守は履修していない者と差がなかった。大学保健管理部門ではサービスに限界があるため、学生のセルフメディケーションを、健康教育などを通じ進めることが求められる

平成19年度の大学における麻疹予防対策 電子メール調査の結果から

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