?梅奧臨床研究人員發(fā)現(xiàn)一基因突變能引起心肌電生理活動紊亂和心房纖維性顫動,，房顫是一種影響上百萬美國老百姓健康的常見心臟節(jié)律紊亂,，能導致心臟心力衰竭與中風發(fā)作,。
??“這個發(fā)現(xiàn)強調(diào)了心房纖顫遺傳易感性的重要性”,，梅奧臨床研究所心血管遺傳學實驗室主任Timothy M. Olson博士解釋道,。
??“確定心房纖顫一個新的分子基礎為個性化診斷和治療心律失常創(chuàng)造了關鍵的一步”,， 梅奧臨床研究所Marriott心臟病研究項目負責人Andre Terzic博士補充道,。這項發(fā)現(xiàn)刊載于7月15日出版的《人類分子遺傳學》雜志,。
??該研究為我們理解先前未知的人體心臟電生理不穩(wěn)定機制提供了一個新的認識。梅奧多學科專家組首次確定了離子通道基因KCNA5的一種特殊類型的突變,，該基因能導致疾病促發(fā)狀態(tài),，稱為離子通道病。
??離子通道病是由于細胞膜上一種特殊微小運輸管道的異常,。這些管道或通道的功能就是選擇性讓某些電荷顆粒出入細胞,，并且通過這種方式使電流通過細胞來調(diào)節(jié)每次心臟搏動。
??KCNA5突變能引起鉀離子通道喪失功能,，擾亂同步電活動,，進而導致心房纖顫的易感性。
??有關房顫的研究
??房顫是世界上最常見的心律失?；虿灰?guī)則心律,。僅在美國就有兩百多萬人罹患此病，造成重大的公共衛(wèi)生問題,。人的一生中,，有25%的可能性患上此病，而患有心房纖顫的病人有5倍的機會染上中風。近年來房顫逐漸被看作是一種遺傳性疾病,。
??在未知心房纖顫危險因素的情況下,，研究人員使用了復雜的基因分析以確定雙胞胎患者DNA的突變。該異?；蛟跓o心房纖顫個體的DNA中是不存在的,。心房纖顫的基因突變發(fā)生在KCNA5基因上，該基因編碼一種關鍵的心臟蛋白質(zhì)Kv1.5,。Kv1.5功能的喪失,，使心房——心臟上部泵血腔室——更易遭受心律紊亂與心房纖顫。
??為驗證該發(fā)現(xiàn),，研究人員在分子,、細胞與器官的水平上復制了該疾病結(jié)構(gòu)，并糾正了該突變,，修復了不正常的電流活動,。
??該研究的主要研究者Drs. Olson 和Terzic說，這項工作在人類遺傳學,、重組DNA技術(shù),、膜片鉗、電生理學與藥物療法等各學科專家的努力下得以實現(xiàn),。
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.
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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.
