The risk stratification of drug-induced long QT syndrome upon the underlying genetics

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hiroshima University (2019); Shiga University of Medical Science (2017-2018)
• Principal Investigator: Itoh Hideki 広島大学, 病院(医), 教授 (30402738)
• Co-Investigator(Kenkyū-buntansha): 大野 聖子 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (20610025) ; 松浦 博 滋賀医科大学, 医学部, 教授 (60238962) ; 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 個別化医療 / 突然死 / 薬剤 / 遺伝子

Outline of Final Research Achievements

This study revealed that patients with drug-induced QT prolongation and/or fatal arrhythmias failed to carry a mutation in minor candidate genes corresponding to congenital long QT syndrome. The frequency of polymorphisms in CYP genes were similar between drug-induced long QT syndrome and normal control cohorts. We are able to establish the risk stratification based on the underlying genetics including LQT1-LQT3, QT interval at baseline, gender and age upon this study.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

薬剤性QT延長症候群の遺伝的背景に、5つの責任遺伝子(KCNQ1:LQT1, KCNH2:LTQ2, SCN5A:LQT3, KCNE1:LQT5, KCNE2:LQT6)以外のminor geneはcontributionが小さいことが明らかになった。薬剤性QT延長症候群の予防・管理においては、保険診療として実施しうるLQT1-3の3つのサブタイプの有無とQT間隔、性別・年齢等を加味した、risk stratificationの構築が実用的であることが示された。