《心脏猝死的修饰基因》

  • 来源专题:心血管疾病防治
  • 编译者: jiafw
  • 发布时间:2018-11-24
  • 基因背景,甚至是完全相同的基因突变,可以呈现多种不同的临床表现,对于这一现象有一种被广泛接受的解释,即存在遗传因子(修饰基因)能够修饰致病突变。本研究主要讨论修饰基因参与改变心律失常风险的概念和原则,并进一步探讨他们导致临床异质性的现有知识和可能解释。在两个重要的与心源性猝死风险相关的临床病症的背景下,我们进行了相关概念的阐述,包括在单基因疾病(先天性长QT综合征)中明确了修饰基因的影响,以及在复杂情况(急性心肌梗死后威胁生命的心律失常)下,寻找心律失常风险的遗传修饰基因更具挑战性。了解修饰基因导致心源性猝死风险较高或较低的进展,能够改善患者特异性的风险分层,并成为迈向精准医学的重要一步。

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  • 《运动员心脏猝死风险》

    • 来源专题:心血管疾病防治
    • 编译者:张燕舞
    • 发布时间:2018-05-22
    • 虽然心脏性猝死(SCD)是运动员死亡的主要医疗原因,但其确切发病率仍不清楚。 到目前为止,最好的估计已经表明,在50,000个运动员年中约有1个发生。 在一项使用加拿大数据库2009年至2014年的数据记录的一项新研究中,该数据库记录了加拿大安大略省所有医院外突发心脏骤停(SCA),运动员SCA的总体速率为每10万运动员年为0.76。 44%的患者在SCA后仍然出院,SCD总发生率为每100,000运动员年0.42。 这些数据表明,运动员SCD的发生率是以前估计的四分之一,并提出了关于预参加筛查的作用的问题。 BACKGROUND The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. METHODS In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. RESULTS Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. CONCLUSIONS In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports. (Funded by the National Heart, Lung, and Blood Institute and others.).
  • 《无损DNA的基因修饰技术》

    • 来源专题:土壤、生物与环境
    • 编译者:李卫民
    • 发布时间:2016-09-01
    • A team involving Kobe University researchers has succeeded in developing 'Target-AID', a genome editing technique that does not cleave the DNA. The technique offers, through high-level editing operation, a method to address the existing issues of genome editing. It is expected that the technique will be applied to gene therapy in the future in addition to providing a powerful tool for breeding useful organisms and conducting disease and drug-discovery research. The findings were published online in Science on August 5. The team consists of Project Associate Professor NISHIDA Keiji and Professor KONDO Akihiko (Graduate School of Science, Technology and Innovation, Kobe University) as well as Associate Professor YACHIE Nozomu (Synthetic Biology Division, Research Center for Advanced Science and Technology, the University of Tokyo) and Professor HARA Kiyotaka (Department of Environmental Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka). Genome editing -- which can directly manipulate the genome information of various organisms without leaving an artificial strand -- has seen rapid progress in recent years and it is gradually becoming a revolutionary tool in fields ranging from life sciences to advanced medical research. Known to be highly effective, genome editing using 'artificial nuclease' aims to cut the DNA at the target point and to modify the gene while it is repaired. As this method is efficacious in biological materials for which genetic operation was difficult, it has been used mainly for higher eukaryotes such as animals and plants. However, a major issue with this method has been the uncertainty of inducing the intended mutation and 'cytotoxicity' caused by splitting of chromosomes. In the present research, researchers demonstrated that it is possible to modify genetic function by inducing target 'point mutation' at a highly efficient rate. The point mutation was induced by forming a synthetic complex through removal of nuclease activity from the CRISPR system -- a technique using artificial nuclease -- and addition of deaminase, a deaminizing (base-modifying) enzyme, and then expressing it in yeasts and mammalian cells. Moreover, it was confirmed that, compared to previous nuclease models, cytotoxicity is significantly reduced by modifying the DNA without cutting. The present technique can realize a more diverse, higher-level genome editing operation as it can efficiently conduct intended modification in a way that does not put significant burden on the cells. It is expected that the new technique will be applied to gene therapy in the future in addition to providing a powerful tool for breeding useful organisms and conducting disease and drug-discovery research. Story Source: The above post is reprinted from materials provided by Kobe University. Note: Content may be edited for style and length