2010 Fiscal Year Annual Research Report
| Project/Area Number |
21659199
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
堀江 稔 滋賀医科大学, 医学部, 教授 (90183938)
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| Co-Investigator(Kenkyū-buntansha) |
上島 弘嗣 滋賀医科大学, 医学部, 特任教授 (70144483)
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| Keywords | 分子心臓病態 |
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| Research Abstract |
QT延長症候群(LQTS)は、著しいQT時間の延長とtorsade de pointesを起こす家族性LQTSは若年者に見られ心臓突然死を起こす。心筋の興奮・伝導・収縮を司る蛋白分子であるイオン・チャネルやその調節蛋白をコードする遺伝子の変異や多型(とくに単一塩基多型=Single Nucleotide Polymorphism以下SNP)が関与している。これらの遺伝的異常のため心筋チャネル蛋白の働きが変化し発症するイオン・チャネル病である。また、従来、SNPは数10から数1000塩基にひとつの頻度で存在し個人の特性を決定するとされたが、最近、病気の発症とも関連する機能的なSNPも知られている。我々は2009年にLQTS関連遺伝子のKCNE1のSNPであるD85Nが、本症の発症に関与することを報告している。このような多様な遺伝的背景を有し、多くは常染色体優性遺伝をするが、実際の臨床現場に遺伝的背景をフィードバックすると、遺伝子変異のキャリアにもかかわらず、LQTSの病像をまったく示さない症例に多く遭遇する。このようなSNP解析モデルとして遺伝子変異が同定されている子供が典型的なQT延長症候群を発症しているにもかかわらず、キャリアの親が35才まで無症候である症例を選択し網羅的なSNP解析を行った。当初、32個の候補SNPについて2人のデータを比較検討することにより、本症の発症を促進する方向に働くSNPと予防的に働くSNPを検索した。これらの研究は、フランス・パリ大学、イタリア・Pavia大学、オランダ・Amsterdam大学の研究室との共同研究のかたちで行った。興味深いことに我々の報告したKCNE1 D85Nがやはり親子モデルでも発症誘因に有意に働くことが判明した。
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Research Products
(57 results)
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[Journal Article] Novel KCNE5 variants are associated with Brugada syndrome and idiopathic ventricular fibrillation.2011
Author(s)
Ohno S, Zankov DP, Ding WG, Itoh H, Makiyama T, Doi T, Shizuta S, Hattori T, Hancox JC, Matsuura H, Horie M
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Journal Title
Circulation Arrhythmia and Electrophysiology
Volume: (in press)
Peer Reviewed
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[Journal Article] A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome.2011
Author(s)
Doi T, Makiyama T, Morimoto T, Haruna Y, Tsuji K, Ohno S, Akao M, Takahashi Y, Kimura T, Horie M
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Journal Title
Circulation : Cardiovascular Genetics
Volume: (in press)
Peer Reviewed
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[Journal Article] QTc prolongation and antipsychotic medication in 1017 patients with schizophrenia.2010
Author(s)
Ozeki Y, Fujii K, Kuromoto N, Yamada N, Okawa M, Aoki T, Takahashi J, Narita M, Ishida N, Saito O, Horie M, Kunugi H.
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Journal Title
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Volume: 34
Pages: 401-405
Peer Reviewed
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[Journal Article] KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders.2010
Author(s)
Wu J, Shimizu W, Ding W-G, Ohno S, Toyada F, Itoh H, Zang W-J, Miyamoto Y, Kamakura S, Matsuura H, Nademanee J, Brugada J, Brugada P, Brugada R, Vatta M, Towbin JA, Antzelevitch C, Horie M.
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Journal Title
Heart Rhythm
Volume: 7
Pages: 199-205
Peer Reviewed
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[Journal Article] Clinical characteristics and genetic background of congenital long QT syndrome diagnosed in fetal, neonatal and infantile life. A nation-wide questionnaire survey in Japan.2010
Author(s)
Horigome H, Nagashima M, Sumitomo N, Yoshinaga M, Ushinohama H, Iwamoto M, Shiono J, Ichihashi K, Hasegawa S, Yoshikawa T, Matsunaga T, Goto H, Waki K, Arima M, Takasugi H, Tanaka Y, Miura M, Ogawa K, Suzuki H, Yamagishi H, Ikoma M, Suda K, Takagi J, Sato J, Shimizu H, Saiki H, Hoshiai M, Ichida F, Takeda S, Takigiku K, Inamura N, Kajino H, Murakami T, Shimizu W, Horie M.
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Journal Title
Circ.Arrhythm Electrophysiol.
Volume: 3
Pages: 10-17
Peer Reviewed
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[Journal Article] High prevalence of early repolarization in short QT syndrome.2010
Author(s)
Watanabe H, Makiyama T, Koyama T, Kannankeril PJ, Seto S, Okamura K, Oda H, Itoh H, Okada M, Tanabe N, Yagihara N, Kamakura S, Horie M, Aizawa Y, Shimizu W.
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Journal Title
Heart Rhythm
Volume: 7
Pages: 674-652
Peer Reviewed
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[Journal Article] A novel SCN5A mutation associated with the linker between III and IV domains of Na(v)1.5 in a neonate with fatal long QT syndrome.2010
Author(s)
Yamamura K, Muneuchi J, Uike K, Ikeda K, Inoue H, Takahata Y, Shiokawa Y, Yoshikane Y, Makiyama T, Horie M, Hara T.Int J Cardiol.
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Journal Title
Int J Cardiol.
Volume: 145
Pages: 61-64
Peer Reviewed
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[Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype : A Japanese multicenter study.2010
Author(s)
Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, T Makiyama, Akao M, Ai T, Noda T, Miyazaki A, Miyamoto Y, Yamagishi M, Kamakura S, Horie M.
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Journal Title
Heart Rythm
Volume: 7
Pages: 1411-1418
Peer Reviewed
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[Journal Article] Atrioventricular block-induced Torsades de Pointes with clinical and molecular backgrounds similar to ongenital long QT syndrome.2010
Author(s)
Oka Y, Itoh H, Ding WG, Shimizu W, Makiyama T, Ohno S, Nishio Y, Sakaguchi T, Akashi M, Kawamura M, Matsuura H, Horie M.
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Journal Title
Circulation Journal
Volume: 17
Pages: 2535-2571
Peer Reviewed
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[Journal Article] Heart rate-dependent variability of cardiac events in type 2 congenital long-QT syndrome.2010
Author(s)
Nagaoka I, Shimizu W, Mizusawa Y, Sakaguchi T, Itoh H, Ohno S, Makiyama T, Yamagata K, Makimoto H, Miyamoto Y, Kamakura S, Horie M.
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Journal Title
Europace
Volume: 12
Pages: 1623-1629
Peer Reviewed
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[Journal Article] Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability.2010
Author(s)
Li P, Ninomiya H, Kurata Y, Kato M, Miake J, Yamamoto Y, Igawa O, Nakai A, Higaki K, Toyoda F, Wu J, Horie M, Shirayoshi Y, Hiraoka M, Hisatome I., Circ Res
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Journal Title
Circ Res.
Volume: 108
Pages: 458-468
Peer Reviewed
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[Presentation] Latent genetic backgrounds and molecular pathogenesis in acquired long QT syndrome with distinct arrhythmic triggers.2010
Author(s)
Itoh H, Oka Y, Ding WG, Sakaguchi T, Kimura H, Mizusawa Y, Miyamoto A, Wu J, Ohno S, Makiyama T, Ito M, Matsuura H, Horie M.
Organizer
AHA Scientific Sessions 2010
Place of Presentation
Chicago Illinois U.S.A.
Year and Date
20101114-20101117
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[Presentation] Carvedilol, an α1- and Non-selective β-adrenoceptor Blocker, for Prevention of Cardiac Events in Patients with Type 2 Long QT Syndrome2010
Author(s)
Kimura H, Itoh H, Mizusawa Y, Miyamoto A, Oka Y, Kawamura M, Nishio Y, Sakaguchi T, Makiyama T, Ito M, Horie M.
Organizer
AHA Scientific Sessions 2010.
Place of Presentation
Chicago Illinois U.S.A.
Year and Date
20101114-20101117
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[Presentation] Roles of fibroblasts in the mechanisms of complex fractionated atrial electrograms and catheter ablation during chronic atrial fibrillation.2010
Author(s)
Ashihara T, Haraguchi R, Nakazawa K, Namba T, Ikeda T, Nakazawa Y, Ozawa T, Itoh H, Ito M, Horie M.
Organizer
APHRS2010/APAFS2010
Place of Presentation
Jeju Island, Korea
Year and Date
20101028-20101030
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[Presentation] Long QT syndrome with compound mutation is associated with a severer phenotype : a Japanese multicenter study.2010
Author(s)
Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Makiyama T, Miyamoto Y, Yamagishi Y, Kamakura S, Horie M.
Organizer
ESC Congress 2010
Place of Presentation
Stockholm, Sweden
Year and Date
20100827-20100901
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