2019 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Shiga University of Medical Science |
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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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| 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 |
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| 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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| Free Research Field |
循環器内科
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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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