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[AHA2013]心房颤动的个体化治疗及其基因组研究注重中国参与——Emelia Benjamin教授专访

作者:  E.Benjamin   日期:2013/11/21 14:18:31

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谢谢您的提问。我认为最重要的是我们已度过由某个科学家在其自己实验室开展相关研究并就给出疾病治疗明确答案的时代。我很赞赏中国同道们在AF方面的工作。上海的陈博士首先研究了可导致AF的基因突变。为促进个体化医疗的实现,世界各地的科学家需共同努力就这些非常复杂的疾病和问题进行研究与探讨。

  Emelia Benjamin教授 波士顿大学医学院

  <International Circulation>: First, I’d like to thank you for the interview today. You just finished chairing a session entitled “personalized medicine: the future of atrial fibrillation management.” Atrial fibrillation (AF) is the most common sustained arrhythmia, which is associated with significant morbidity and mortality. However, the mechanisms and pathophysiology of AF treatments are often unsatisfactory. What do you think of the prospects of the Personalized Medicine in the AF Management? And what should we do to achieve that purpose?

  Prof. Benjamin: Thank you for the question. I think first and foremost, we are past the era where single scientists can go into his/her lab and figure out the cure or definitive answer to anything. I applaud my colleagues in China for their work on AF. The first person to describe the genetic mutation leading to AF was Dr. Chen in Shanghai. What we’re increasingly appreciating is that in order to make the reality of personalized medicine come to pass, we need to have international consortia of scientists working on these very complex diseases and problems together. I think there are multiple opportunities for prevention, nearest to my heart as an Epidemiologist, is the prevention of the onset of AF. We have an international consortium in which we have developed a risk prediction model and validated it. That study was originally lead by Dr. Aletto Alonso from the ERIC study, we brought along cohort studies and really do a reasonably good job of predicting incident AF. The hope, of course, is that as we get more refined in our ability to predict AF, we will be more successful in developing targets (drug, therapeutic, lifestyle) to prevent its onset. The follow up to that is the prevention of the recurrence of AF once it’s happened (secondary prevention) and most importantly, the prevention of the complications. There’s been a lot of elegant work in these areas.

  I would say that unfortunately, there’s been much less epidemiologic groundwork in China on AF. There have been a number of studies that have looked at prevalence of AF. The Guangzhou cohort and others are starting to look at what predicts incident AF in people of Chinese ancestry? Also, very interested to start developing genetic/genomic markers that the risk factors like hypertension, heart failure, etc., are very likely to translate across ethnicity and race. More fundamental are the genetic mechanisms. Those may have some overlap but there will be some variation and that will really require collaboration with Chinese colleagues working on Chinese samples so we can be relevant to that (Chinese) population.

  《国际循环》:首先,非常感谢您接受今天的采访。您主持了刚刚结束的“个体化医学:心房颤动管理之未来”专题。心房颤动(AF)是最常见的持续性心律失常,发病率及死亡率极高。但目前其治疗机制及病理生理学尚未完全阐明。您如何看待AF的个体化治疗前景?要想实现AF管理的个体化,我们尚有哪些工作要做?

  Benjamin教授:谢谢您的提问。我认为最重要的是我们已度过由某个科学家在其自己实验室开展相关研究并就给出疾病治疗明确答案的时代。我很赞赏中国同道们在AF方面的工作。上海的陈博士首先研究了可导致AF的基因突变。为促进个体化医疗的实现,世界各地的科学家需共同努力就这些非常复杂的疾病和问题进行研究与探讨。我认为,作为流行病学家,我们有很多方式可预防AF发作。有个国际工作组已开发出一种风险预测模型,并对其进行验证。这方面的研究最初是由参与ERIC研究的Aletto Alonso牵头。我们开展了大量队列研究,做了相当不错的工作预测AF发生。当然,我们希望能更精确地预测AF,更成功地通过药物及生活方式干预预防AF发作。一旦AF发生,则需预防其复发(即二级预防),其中最重要的是预防并发症发生。我们在这些领域已做了大量工作。但我想说的是,不幸的是,中国AF的流行病学研究基础较薄弱。有很多研究观察了AF患病率,其中广州的队列研究及其他研究正在探讨中国人群中能预测AF发生的因素。此外,中国研究者正在积极研发各种族及民族共同的高血压及心力衰竭等的遗传/基因标志物。其中有些更基础的研究探讨了AF发病的遗传机制。这些研究之间可能存在重叠,但也有所不同。这需要中国同道们真正地合作研究中国样本。

  <International Circulation>: The result of Framingham Heart Study showed that genetic loci associated with atrial fibrillation had limited relation to left atrial structure. What do you think of this result and the future clinical prospects of genetics and genomics in the treatment of AF?

  Prof. Benjamin: That’s a great question. The reality is that we now have 9 published loci that are related to new-onset AF and related to prevalent AF. We do not truly understand all of the mechanisms behind those loci. Science takes time. When you think about many of the fundamental discoveries, from discovery to drug, it often takes 5, 10 up to 20 years. I think that hopefully, as we better understand the mechanisms underlying the loci, we will develop drug targets that will be of service to patients.

  《国际循环》:Framingham心脏研究结果显示,与AF相关的基因位点与左心房结构的相关性有限。您如何看待这一结果以及AF基因及基因组学研究在其治疗中的临床应用前景?

  Benjamin教授:这是非常好的问题。现实情况是我们现在已发现9个与新发AF及AF患病相关的基因位点。但尚不真正了解这些基因位点的作用机制,阐明其具体机制尚需时间。你可以回顾一下,很多科学发现从最初发现到研发相关药物,通常需要5年、10年甚至20年。我认为如果能更好地理解基因位点作用的相关机制,将非常有希望研发以其为靶标的药物,为广大患者服务。

  <International Circulation>: Congratulations to you on winning the FGTB Mentoring Award. Would you please talk about the importance of good mentorship for the clinical practice? And what do you think are the main elements of a good clinical mentorship?

  Prof. Benjamin: I think the most important concept that has emerged literally from business literature is the understanding that medicine, academics, even businesses are so complex that the old vision of one single mentor, the dyadic mentor, where you had the typically father looking at the prodigal son, is really an outdated concept. To have a successful career in academics or clinical practice, it requires a mentoring network of multiple individuals with different expertise that can advise you throughout various aspects of your career. For instance, I went to one person who helped me write my first grant, then another to strategize how to deal with complex political situations in my university. Another person, Gary Ballidy, has mentored me in how to become involved in the American Heart Association. One thing I would like to draw to your attention and those of your readership, the AHA is keenly interested in expanding and collaborating with our international colleagues. We particularly see an opportunity to invest and connect with early career colleagues around the world and I know for a fact that China is one of our key areas of interest. My council (functional genomics and translational biology) and many others has mentoring programs one can go online, connect with a mentor, typically it will help if you speak some English because most do not speak Chinese. Although frankly, most young Chinese people that I meet speak and write English better than many of my American colleagues. We are keenly interested in developing longitudinal relationships with our colleagues in China. I will send the link where you can sign up, and what will happen logistically is that we will meet with people at the meeting and introduce them to people. I would encourage your young investigators to apply for our Functional Genomics and Translational Biology Young Investigator Award because it’s very prestigious but also because it gives you a connection to the AHA.

  《国际循环》:首先祝贺您荣获FGTB指导奖。良好的师徒关系对临床实践有何重要意义?在临床上,确保良好师徒关系的要素有哪些?

  Benjamin教授:我认为最重要的是要知道医疗、学术及企业之间具有非常复杂的关系,原来类似父子关系的单一导师制已过时。要想在学术及临床实践方面拥有成功的职业生涯,需要具有不同专长的人组织构建一个良好的指导网络,指导职业生涯的各个方面。例如,在大学里有人会帮我申请第一个基金,有人会教我如何制订相关策略以应对复杂局面,而Gary Ballidy则指导我如何成为美国心脏协会会员。有件事情我想特别向你和你们的读者强调,AHA非常积极致力于与国际同道合作。我们尤其发现在早期职业生涯发展方面与世界各地具有合作机会,据我所知,中国是我们非常想合作的国家之一。我所在的功能基因组学及转化生物学理事会及其他理事会都有相应的辅导方案,你可以网上在线与导师联系,如果你能说英语就更好了。因为大多数导师不会说汉语。坦率地说,我所遇到的大多数年轻中国人用英文交流和写作的能力要比我的美国同道好得多。我们非常有兴趣与中国同道发展纵向合作关系,我将把注册网址发给你,在本届大会上我们也会将其介绍给参会者。我鼓励年轻研究者申请我们的功能基因组学与转化生物学青年研究者奖,因为这个奖项不仅非常有名,还能加强你与AHA的联系。

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心房颤动基因组研究ERIC研究二级预防

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