| 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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| Budget Amount *help |
¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000)
Fiscal Year 2005: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2004: ¥40,560,000 (Direct Cost: ¥31,200,000、Indirect Cost: ¥9,360,000)
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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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