2005 Fiscal Year Final Research Report Summary
Molecular Medicine of Inherited Arrhythmias : Clinical application of genetic analysis
| Project/Area Number |
16209025
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
HORIE Minoru Shiga University of Medical Science, Professor, 医学部, 教授 (90183938)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Hiroshi Shiga University of Medical Science, Professor, 医学部, 教授 (60238962)
KOMORI Masaru Shiga University of Medical Science, Professor, 医学部, 教授 (80186824)
AKAO Masaharu Kyoto University, Graduate School of Medicine, Assistant, 大学院・医学研究科, 助手 (00362509)
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| Project Period (FY) |
2004 – 2005
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| Keywords | long QT syndrome / genetic analysis / Brugada syndrome / drug-induced QT prolongation / CPVT / ARVC / mutation / single nucleotide polymorphism |
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| Research Abstract |
During last two decades our understanding for inherited types of arrhythmias has been advanced enormously as a result of evolutionary progress in molecular genetics and electrophysiology. Starting from the long QT syndrome (LQTS), genetic variants in genes encoding ion channels and their accessory proteins have been shown to cause a variety of hereditary disorder of heart rhythm such as Brugada syndrome, familial sick sinus syndrome, catecholeminergic polymorphic ventricular tachycardia (CPVT), and even familial atrial fibrillation. These diseases are now classified under the category as the cardiac ion channelopathy. Among them, the LQTS played a key role as the "Rosetta Stone", because a number of studies on LQTS patients unveiled major mechanisms underlying the ion channelopathy. Scince the year of 1996, we have been conducting genetic test of LOQTS-related genes in patients with hereditary arrhythmias, including LQTS, Brugada syndrome, CPVT, arrhythmogenic right ventricular cardiomyo-pathy (ARVC), and other types of arrhythmias associated with inherited heart diseases. In addition, we also examined the patients with secondary LQTS. To date, eight distinct genes responsible for LQTS have been found including those for Andersen (LQT7) and Timothy (LQT8) syndromes on chromosome ; 11q15.5 (KCNQ1 ; LQT1), 7q35-36 (KCNH2 ; LQT2), 3p21 (SCN5A ; LQT3), 4q25-27 (ANKB ; LQT4), 21q22 (KCNE1 ; LQT5), 21q22 (KCNE2 ; LQT6), 17q23 (KCNJ2 ; LQT7) and 12p13.3 (CACN1c ; LQT8). Our cohort now contains more than 300 individuals with LQTS and ~100 with other types of inherited arrhythmias. We also conducted the biophysical functional assay resultant from the mutations in candidate genes, and our results in this cohort have been published in several world-known journals as summarized below.
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[Journal Article] The Jervell and Lange-Nielsen Syndrome. Molecular basis, natural history, and clinical outcome.2006
Author(s)
Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Denjoy I, Schulze-Bahr E, Amlie JP, Timothy K, Shkolnikova M, Berul C, Bitner-Glindzicz M, Toivonen L, Horie M.
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Journal Title
Circulation 113
Pages: 783-790
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations : characteristic T-U-wave patterns predict the KCNJ2 genotype.2005
Author(s)
Zhang L, Benson DW, Tristani-Firouzi M, Ptacek LJ, Tawil R, Schwartz PJ, George AL, Horie M, Andelfinger G, Snow GL, Fu YH, Ackerman MJ, Vincent GM.
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Journal Title
Circulation 111
Pages: 212720-212726
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High-risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.2005
Author(s)
Makiyama T, Akao M, Tsuji K, Doi T, Ohno S, Takenaka K, Kobori A, Ninomiya T, Yoshida H, Takano T, Makita N, Yanagisawa F, Higashi Y, Takeyama Y, Kita T, Horie M
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Journal Title
Journal of American College of Cardiology 46
Pages: 2100-2106
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cellular and ionic mechanism for drug-induced long QT syndrome and effectiveness of verapamil.2005
Author(s)
Aiba T, Shimizu W, Inagaki M, Noda T, Miyoshi S, Ding W-G, Zankov DP, Toyoda F, Matsuura H, Horie M, Sunagawa K.
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Journal Title
Journal of American College of Cardiology 45
Pages: 300-307
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 Form of congenital long QT syndrome2004
Author(s)
Shimizu W, Horie M, Ohno S, Takenaka K, Yamaguchi M, Shimizu M, Washizuka T, Aizawa T, Nakamura K, Ohe T, Aiba T, Miyamoto Y, Yoshimasa Y, Towbin J, Priori S, Kamakura S
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Journal Title
Journal of American College of Cardiology 1
Pages: 117-125
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Additional gene variants reduce effectiveness of Beta-Blockers in the LQT1 form of long QT syndrome2004
Author(s)
Kobori A, Sarai N, Shimizu W, Nakamura Y, Murakami Y, Makiyama T, Ohno S, Takenaka K, Ninomiya T, Fujiwara Y, Matsuoka S, Takano M, Noma A, Kita T, Horie M
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Journal Title
Journal of Cardiovascular Electrophysiology 15
Pages: 1-10
Description
「研究成果報告書概要(欧文)」より
