Genetic variants of alcohol metabolizing enzymes in Cardiovascular Disorders
Project/Area Number |
17K09495
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Shiga University of Medical Science |
Principal Investigator |
Hayashi Hideki 滋賀医科大学, 医学部, 非常勤講師 (70464188)
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Co-Investigator(Kenkyū-buntansha) |
堀江 稔 滋賀医科大学, アジア疫学研究センター, 特任教授 (90183938)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | アルコール代謝酵素 / 遺伝子多型 / ブルガダ症候群 / 心室細動発作 / ADH1B / ALDH2 / 循環器・高血圧 / 遺伝子 / 不整脈 / 遺伝 / ADH1B遺伝子 / ALDH2遺伝子 / アセトアルデヒド / 酵素 / アルコール / アルコール依存症 / 突然死 |
Outline of Final Research Achievements |
Patients with Brugada syndrome (BrS) are known to have arrhythmic events after alcohol drinking and recommended to avoid its excessive intake.This study aimed to test the hypothesis whether activity of alcohol‐metabolizing enzymes determines cardiac events after drinking alcohol and comprized 198 BrS patients: 90 symptomatic and 108 asymptomatic, and the symptomatic was divided into 16 alcohol‐related and 74 alcohol‐unrelated group.SNPs of two genes: alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) were determined.The SNP distribution for ADH1B was not significantly different between symptomatic and asymptomatic groups, but the genotype ADH1B His/His was significantly more prevalent in the alcohol‐related group than in the unrelated (81.3% vs 50%, P = .023). In multivariate logistic regression, the ADH1B His/His was independently associated with syncope after alcohol (odds ratio, 5.746; P = .007), indicating the relation between cardiac events and ADH1B SNP.
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Academic Significance and Societal Importance of the Research Achievements |
循環器疾患でも、アルコール摂取と発症との関連が知られている病気に、ブルガダ症候群がある。2013年の Expert Consensus Statementでは、過剰なアルコール摂取は、心イベントの引き金になるとされるが、体内に入ったアルコールが、なぜ致命的な不整脈を引き起こすのかは不明である。本研究では、アルコール代謝に関わるADH1BとALDH2の2つの酵素をコードする遺伝子のSNP遺伝型が、血中アセトアルデヒド・レベルを変化させ、自律神経に影響する結果、ブルガダ症候群患者の致死的な不整脈を誘発する可能性を明らかにした。この遺伝型は、東アジア人に多く本症の発症頻度との関連からも興味深い。
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] Co-phenotype of left ventricular noncompaction cardiomyopathy and atypical catecholaminergic polymorphic ventricular tachycardia in association with R169Q, a ryanodine receptor type 2 gene missense mutation.2020
Author(s)
Nozaki Y, Kato Y, Uike K, Yamamura K, Kikuchi M, Yasuda M, Ohno S, Horie M, Murayama T, Kurebayashi N, Horigome H.
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Journal Title
Circ J
Volume: 2
Pages: 226-234
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term prognosis of patients with J-wave syndrome.2020
Author(s)
Kamakura T, Shinohara T, Yodogawa K, Murakoshi N, Morita H, Takahashi N, Inden Y, Shimizu W, Nogami A, Horie M, Aiba T, Kusano K.
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Journal Title
Heart
Volume: 106
Issue: 4
Pages: 299-306
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation.2019
Author(s)
Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
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Journal Title
Circulation
Volume: In press
Issue: 18
Pages: 2157-2169
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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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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[Journal Article] Guidelines for Heart Disease Screening in Schools (JCS 2016/JSPCCS 2016) ― Digest Version ―2018
Author(s)
umitomo N, Baba R, Doi S, Higaki T, Horie M, Nagashima M, Niwa K, Ogawa S, Okumura K, Tsutsui H (et al. )
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Journal Title
Circulation Journal
Volume: 82
Issue: 9
Pages: 2385-2444
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2018-08-24
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of Coronary Artery Calcification with Estimated Coronary Heart Disease Risk from Prediction Models in a Community-Based Sample of Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)2018
Author(s)
Tai P, Fujiyoshi A, Arima H, Tanaka-Mizuno S, Hisamatsu T, Kadowaki S, Kadota A, Zaid M, Sekikawa A, Yamamoto T, Horie M, Miura K, Ueshima H
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 25
Issue: 6
Pages: 477-489
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2018-06-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men2018
Author(s)
Suzuki S, Arima H, Miyazaki S, Fujiyoshi A, Kadota A, Takashima N, Hisamatsu T, Kadowaki S, Zaid M, Torii S, Horie M, Murata K, Miura K, Ueshima H
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 25
Issue: 2
Pages: 186-198
DOI
NAID
ISSN
1340-3478, 1880-3873
Related Report
Peer Reviewed / Open Access
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[Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.2018
Author(s)
Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
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Journal Title
Br. J. Clin. Pharmacol.
Volume: -
Issue: 6
Pages: 1301-1312
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[Journal Article] SCN5A mutations in 442 neonates and children: genotype?phenotype correlation and identification of higher-risk subgroups2018
Author(s)
30.Baruteau A, Kyndt F, Behr ER, MD, Vink AS, Lachaud M, Joong A, Schott J-J, Horie M, Wilde AA, Schwartz PJ, Probst V. (et al.)
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Journal Title
European Heart Journal
Volume: 39
Issue: 31
Pages: 2879-2887
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.2017
Author(s)
Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau AE, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin JP, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura KI, Redon R, Schott JJ, Makita N.
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Journal Title
J Am Coll Cardiol.
Volume: 70
Issue: 3
Pages: 358-370
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Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers.2017
Author(s)
Nishiuchi S, Makiyama T, Aiba T, Nakajima K, Hirose S, Kohjitani H, Yamamoto Y, Harita T, Hayano M, Wuriyanghai Y, Chen J, Sasaki K, Yagihara N, Ishikawa T, Onoue K, Murakoshi N, Watanabe I, Ohkubo K, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, et.al
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Journal Title
Circ Cardiovasc Genet.
Volume: 6
Issue: 6
DOI
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[Journal Article] Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.2017
Author(s)
Li, M., Kanda, Y., Ashihara, T., Sasano, T., Nakai, Y., Kodama, M., Hayashi, E., Sekino, Y., Furukawa, T., and Kurokawa, J.
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Journal Title
J. Pharm. Sci.
Volume: 134
Issue: 2
Pages: 75-85
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