?梅奥临床研究人员发现一基因突变能引起心肌电生理活动紊乱和心房纤维性颤动，房颤是一种影响上百万美国老百姓健康的常见心脏节律紊乱，能导致心脏心力衰竭与中风发作。
??“这个发现强调了心房纤颤遗传易感性的重要性”，梅奥临床研究所心血管遗传学实验室主任Timothy M. Olson博士解释道。
??“确定心房纤颤一个新的分子基础为个性化诊断和治疗心律失常创造了关键的一步”， 梅奥临床研究所Marriott心脏病研究项目负责人Andre Terzic博士补充道。这项发现刊载于7月15日出版的《人类分子遗传学》杂志。
??该研究为我们理解先前未知的人体心脏电生理不稳定机制提供了一个新的认识。梅奥多学科专家组首次确定了离子通道基因KCNA5的一种特殊类型的突变，该基因能导致疾病促发状态，称为离子通道病。
??离子通道病是由于细胞膜上一种特殊微小运输管道的异常。这些管道或通道的功能就是选择性让某些电荷颗粒出入细胞，并且通过这种方式使电流通过细胞来调节每次心脏搏动。
??KCNA5突变能引起钾离子通道丧失功能，扰乱同步电活动，进而导致心房纤颤的易感性。
??有关房颤的研究
??房颤是世界上最常见的心律失常或不规则心律。仅在美国就有两百多万人罹患此病，造成重大的公共卫生问题。人的一生中，有25%的可能性患上此病，而患有心房纤颤的病人有5倍的机会染上中风。近年来房颤逐渐被看作是一种遗传性疾病。
??在未知心房纤颤危险因素的情况下，研究人员使用了复杂的基因分析以确定双胞胎患者DNA的突变。该异常基因在无心房纤颤个体的DNA中是不存在的。心房纤颤的基因突变发生在KCNA5基因上，该基因编码一种关键的心脏蛋白质Kv1.5。Kv1.5功能的丧失，使心房——心脏上部泵血腔室——更易遭受心律紊乱与心房纤颤。
??为验证该发现，研究人员在分子、细胞与器官的水平上复制了该疾病结构，并纠正了该突变，修复了不正常的电流活动。
??该研究的主要研究者Drs. Olson 和Terzic说，这项工作在人类遗传学、重组DNA技术、膜片钳、电生理学与药物疗法等各学科专家的努力下得以实现。
英文原文：
Mayo Clinic researchers discover a genetic cause for atrial fibrillation
Rochester, Minn. -- Mayo Clinic investigators have discovered a gene mutation causing chaotic electrical activation of the heart muscle and atrial fibrillation (AF), a common heart-rhythm disturbance affecting millions of Americans. Atrial fibrillation can lead to heart failure and stroke.
"The discovery underscores the significance of heredity in susceptibility to atrial fibrillation," explains Timothy M. Olson, M.D., director of the Cardiovascular Genetics Laboratory at Mayo Clinic.
"Identification of a new molecular basis for atrial fibrillation provides a critical step toward individualized diagnosis and treatment of arrhythmia," adds Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Marriott Heart Disease Research Program.
The Mayo Clinic discovery is published in the July 15 issue of the journal Human Molecular Genetics (http://hmg.oxfordjournals.org/cgi/content/full/15/14/2185).
Significance of the Mayo Clinic Research
The Mayo Clinic study provides new insight into a previously unrecognized mechanism for electrical instability in the human heart. The Mayo multidisciplinary team is the first to identify a specific genetic mutation of the ion channel gene KCNA5 that leads to a disease-causing condition called a channelopathy.
A channelopathy is an abnormality of specific miniature transportation tubes in cell membranes. The job of these tubes -- or channels -- is to selectively allow certain charged particles in and out of the cell, and in this way, pass electrical currents in and out of the cell to regulate each heartbeat. The KCNA5 mutation causes loss of function of an atrial-specific potassium ion channel, disrupting electrical synchronization. This leads to susceptibility for atrial fibrillation.
About Atrial Fibrillation
Atrial fibrillation is the most common arrhythmia -- or irregular heartbeat -- worldwide. In the United States alone, more than 2 million Americans suffer from atrial fibrillation, constituting a major public health epidemic. During a person's lifetime, there is a 25 percent risk this rhythm disorder will develop, and patients with atrial fibrillation have a fivefold increased risk for stroke. Atrial fibrillation has been increasingly recognized as an inherited disease.
About the Study
The Mayo investigation used comprehensive genetic analysis to identify a mutation in the DNA of a sibling pair with atrial fibrillation in the absence of known risk factors for the disease. This genetic anomaly was not present in the DNA of individuals without atrial fibrillation.
The atrial fibrillation mutation occurred in the KCNA5 gene, which produces a key heart protein known as Kv1.5. Loss of Kv1.5 function, in turn, made the atria -- the upper pumping chambers of the heart -- more vulnerable to stress-induced chaotic rhythms, and atrial fibrillation.
To validate the finding, the researchers reproduced the disease features at the molecular, cellular and organism levels and corrected the mutation, restoring the defective ionic current.
###
Drs. Olson and Terzic, the principal investigators of the study, said this work was made possible through the efforts of a multidisciplinary team integrating human genetics, recombinant DNA technology, patch-clamp electrophysiology and pharmacotherapy.
Collaboration and Support
The Mayo Clinic collaborative team also included Alexey Alekseev, Ph.D.; Xiaoke Liu, M.D., Ph.D.; Sungjo Park, Ph.D.; Leonid Zingman, M.D.; Martin Bienengraeber, Ph.D.; Srinivasan Sattiraju, M.D.; Jeffrey Ballew; and Arshad Jahangir, M.D. Their work was supported by grants from the National Institutes of Health, Marriott Heart Disease Research Program, Marriott Foundation and Mayo Clinic.
To obtain the latest news releases from Mayo Clinic, go towww.mayoclinic.org/news. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories. For more on Mayo Clinic research, go to www.mayo.edu.
