Elucidation of genetic predispositions to cardiac sudden death in Brugada syndrome
Project/Area Number |
18K15894
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | National Cardiovascular Center Research Institute (2019) Nagasaki University (2018) |
Principal Investigator |
ISHIKAWA TAISUKE 国立研究開発法人国立循環器病研究センター, オープンイノベーションセンター, 室長 (60708692)
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Project Period (FY) |
2018-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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Keywords | 心臓突然死 / ブルガダ症候群 / リスク層別化 / 次世代シーケンス / ブルガダ症候群患者 / ゲノム / SNP / 突然死 / プレシジョンメディスン / リスク予測 / 致死性不整脈 / ゲノムワイド関連解析 / 一次予防 / リスク階層化 |
Outline of Final Research Achievements |
There is no definitive methods to estimate the risk of sudden cardiac death in Brugada syndrome (BrS), which is characterized by nocturnal fetal arrhythmia among middle-aged men. To identify the genetic variants for the sudden death, we performed a Genome-Wide Association Study on 752 Japanese BrS patients and 1146 Japanese controls, and found multiple risk variants for sudden death. Since it was not replicated in other races, we considered the variant to increase the risks of sudden death race-specifically. We next performed deep sequencing around the sudden death risk variant in Japanese BrS patients and found candidate variants associated with sudden death. We are now conducting experiments on the cellular system to elucidate the molecular mechanisms that link variants to the risk of sudden death.
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Academic Significance and Societal Importance of the Research Achievements |
ブルガダ症候群(BrS)は中年男性に好発する心臓突然死だが、誰にいつ起こるか予測する手法がない。BrSには家族歴が認められ遺伝する側面があることからゲノムに心臓突然死のリスクを予期するものがあると考え、BrSと対称群のゲノムワイド関連解析を行って突然死リスクに関連するSNPを複数同定した。この結果は他人種では再現されなかったため日本人特異的であると考えた。周辺配列をシーケンスすると、この日本人らしさに関与すると思われるバリアントを複数同定した。現在これらがどのようにして心臓突然死に関与するか明らかにする実験を進めており、これによって突然死予防法の確立につながると考えられる。
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway2020
Author(s)
Miyao N., Hata Y., Izumi H., Nagaoka R., Oku Y., Takasaki I., Ishikawa T., Takarada S., Okabe M., Nakaoka H., Ibuki K., Ozawa S., Yoshida T., Hasegawa H., Makita N., Nishida N., Mori H., Ichida F., Hirono K.
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Journal Title
PLOS ONE
Volume: 15
Issue: 4
Pages: 0227393-0227393
DOI
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Peer Reviewed / Open Access
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[Journal Article] Desmin‐related myopathy characterized by non‐compaction cardiomyopathy, cardiac conduction defect, and coronary artery dissection2020
Author(s)
Tamiya R., Saito Y., Fukamachi D., Nagashima K., Aizawa Y., Ohkubo K., Hatta T., Sezai A., Tanaka M, Ishikawa T., Makita N., Sumitomo N., Okumura Y.
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Journal Title
ESC Heart Failure
Volume: -
Issue: 3
Pages: 1338-1343
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of transmembrane protein 168 mutation in familial Brugada syndrome.2020
Author(s)
Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H.
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Journal Title
FASEB Journal
Volume: 34
Issue: 5
Pages: 6399-6417
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pathological Features of Lamin Cardiomyopathy2020
Author(s)
Kawano, H., Ishimatsu, T., Ishijima, I., Hayashi, T., Ishikawa, T., Makita, N., Maemura,K.
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Journal Title
Circulation Journal
Volume: -
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Manifestations and Long-Term Mortality in <i>Lamin A/C</i> Mutation Carriers From a Japanese Multicenter Registry2018
Author(s)
14.Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Kato K, Yamamoto Y, Doi T, Shizuta S, Onoue K, Yagihara N, Ishikawa T, Watanabe I, Kawakami H, Oginosawa Y, Murakoshi N, Nogami A, Aonuma K, Saito Y, Kimura T, Yasuda S, Makita N, Shimizu W, Horie M, Kusano K.
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Journal Title
Circulation Journal
Volume: 82
Issue: 11
Pages: 2707-2714
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2018-10-25
Related Report
Peer Reviewed / Open Access
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[Presentation] 患者由来iPS 細胞モデルを用いたCav 1.2イオン選択性を障害するCACNA1C-E1115K変異がQT 延長症候群、Brugada 症候群を発症するメカニズムの解析2020
Author(s)
柏麻美, 牧山武, 糀谷泰, マウリッセン トーマス, ウリヤンハイ イミン, 山本雄大, ガオ ジンシャン, ファン ハイ, 今村知彦, 相澤卓範, 石川泰輔, 大野聖子, 豊田太, 佐藤誠一, 高橋一浩, ウォルツェン クヌート, 堀江稔, 蒔田直昌, 木村剛
Organizer
第97回日本生理学会大会
Related Report
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[Presentation] 次世代シーケンス解析による特発性心室細動の遺伝背景の解明2019
Author(s)
謝颯琴, 高橋篤, 大野聖子, 鎌倉令, 石川泰輔, 植田初江, 斯波真理子, 南野直人, 林研至, 八木原伸江, 中野由紀子, 伊藤英樹, 宮本恵宏, 田中敏博, 蒔田直昌, 堀江稔, 清水渉, 草野研吾, 安田聡, 相庭武司
Organizer
日本人類遺伝学会第64回大会
Related Report
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[Presentation] Single Cell Electrophysiological Analysis of iPS Cell-Derived Cardiomyocytes Generated from Long-QT Syndrome Patients Carrying a CALM2 Mutation Using a Membrane Potential Imaging System2019
Author(s)
Yamamoto Y., Makiyama T., Wuriyanghai Y., Kohjitani H., Hirose S., Gao J., Kashiwa A., Huang H., Ishikawa T., Ohno S., Chonabayashi K., Suda K., Yoshida Y., Horie M., Makita N., Kimura T.
Organizer
第66回日本不整脈心電学会
Related Report
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[Presentation] Modeling Overlapping Phenotypes of Long-QT and Brugada Syndrome with CACNA1C-E1115K that Alters Ion Selectivity of the Cardiac L-Type Calcium Channel Using Induced Pluripotent Stem Cells2019
Author(s)
Kashiwa A., Makiyama T., Kohjitani H., Hirose S., Gao J., Kashiwa A., Huang H., Ishikawa T., Ohno S., Chonabayashi K., Suda K., Yoshida Y., Horie M., Makita N., Kimura T.
Organizer
第66回日本不整脈心電学会
Related Report
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[Presentation] Modeling Overlap Syndrome of Long QT and Brugada Syndrome Associated with Induced Pluripotent Stem Cells2019
Author(s)
Kashiwa A., Makiyama T., Kohjitani H., Wuriyanghai Y., Yamamoto Y., Jungshan G., Huang H., Ishikawa T., Ohno S., Toyoda F., Sato S., Horie M., Makita N., Kimura T.
Organizer
The 40th Heart Rhythm Society Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Cardiac Emerinopathy, Novel Nonsyndromic Xlinked Left Ventricular Noncompaction Associated With Progressive Atrial Conduction Disturbance2019
Author(s)
Ishikawa T., Barc J., Mishima H., Hirono K., Terada S., Kowase S., Sato T., Mukai Y., Yui Y., Ohkubo K., Kimoto H., Hata Y., Aiba T., Ohno S., Chishaki A., Shimizu W., Horie M., Ichida F., Nogami A., Yoshiura K., Schott JJ., Makita N.
Organizer
The 40th Heart Rhythm Society Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Rare Coding Variants in Genes Other Than SCN5A Are Minimal Genetic Burden on the Prognosis of Brugada Syndrome2018
Author(s)
Ishikawa T, Mishima H, Ohno S, T. A, Nakano Y, Aizawa Y, Nakajima T, Hayashi K, Murakoshi N, Yagihara N, Kimoto H, Makiyama T, Watanabe H, Morita H, Yoshiura K, Nogami A, Shimizu W, Horie M, Tanaka T and Makita N.
Organizer
The 65th Annual Meeting of the Japan Heart Rhythm Society
Related Report
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[Presentation] Clinical Manifestations and Long-term Mortality in Lamin A/C Mutation Carriers from the Japanese Multicenter Registry2018
Author(s)
Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Doi T, Shizuta S, Onoue K, Yagihara N, Ishikawa T, Watanabe I, Oginosawa Y, Nogami A, Aonuma K, Saitoh Y, Kimura T, Makita N, Shimizu W, Horie M and Kusano K.
Organizer
The 65th Annual Meeting of the Japan Heart Rhythm Society
Related Report
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[Presentation] The inactivation of L-type Ca2+ Channel was impaired in Human iPS Cell Model of Long-QT Syndrome with CALM2-D134H Mutation.2018
Author(s)
Yamamoto Y, Makiyama T, Harita T, Hayano M, Nishiuchi S, Wuriyanghai Y, Kohjitani H, Hirose S, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Suda K, Yoshida Y, Horie M, Makita N and Kimura T.
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] Single Cell Electrophysiological Analysis of Human iPS Cell-Derived Cardiomyocytes Generated from Long-QT Syndrome Patients Carrying a CALM2 Mutation Using a Membrane Voltage Imaging System2018
Author(s)
Yamamoto Y, Makiyama T, Wuriyanghai Y, Kohjitani H, Hirose S, Gao J, Kashiwa A, Kimura T, Ishikawa T, Motomura H, Makita N, Ohno S, Chonabayashi K, Yoshida Y, Suda K and Horie M.
Organizer
The 11th Asia Pacific Heart Rhythm Society Scientific Session
Related Report
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[Book] 循環器科の心電図2018
Author(s)
村川 裕二
Total Pages
224
Publisher
南江堂
ISBN
9784524237913
Related Report
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