Roberts Robert
University of Ottawa Heart Institute, ON, Canada.
Nat Clin Pract Cardiovasc Med. 2006 May;3(5):276-82. doi: 10.1038/ncpcardio0509.
Atrial fibrillation is the most common cardiac arrhythmia, and it increases in prevalence with advancing age to about 6% in people older than 65 years. The chance of developing atrial fibrillation at age 40 years or older is about 25% in men and women. This arrhythmia accounts for about one-third of all strokes, and 30% of all patients with atrial fibrillation have a family history of the disease. In 1997, Brugada et al. identified the first locus for familial atrial fibrillation on chromosome 10q22-24 in three different Spanish families. Since that time, seven further loci have been mapped and four relevant genes identified. All these genes encode potassium-channel subunits. The mechanism of action by which all four genes induce atrial fibrillation is via shortening of the action potential duration and atrial effective refractory period. The consistency of the mechanism of action beckons the development of therapy specifically targeted to prevent these molecular events. In addition to monogenic diseases, patients with structural heart disease are predisposed to atrial fibrillation by inherited DNA polymorphisms. The development of chips with hundreds of thousands of single-nucleotide polymorphisms to perform genome-wide scans will elucidate over the next few years the single-nucleotide polymorphisms that predispose to atrial fibrillation. Within the next decade, most of the genes responsible for atrial fibrillation and the single-nucleotide polymorphisms that confer predisposition will probably be identified, and therapies will be developed on the basis of individuals' genomic profiles. In this review I provide an overview of the understanding of the relevant genetic mutations that have been identified so far, and briefly discuss what implications this information might have for practice.
心房颤动是最常见的心律失常，其患病率随年龄增长而增加，65岁以上人群中约为6%。40岁及以上男性和女性发生心房颤动的几率约为25%。这种心律失常约占所有中风的三分之一，30%的心房颤动患者有该病的家族史。1997年，Brugada等人在三个不同的西班牙家族中确定了10q22 - 24染色体上家族性心房颤动的首个基因座。从那时起，又确定了另外七个基因座并鉴定出四个相关基因。所有这些基因都编码钾通道亚基。这四个基因诱发心房颤动的作用机制是通过缩短动作电位时程和心房有效不应期。作用机制的一致性促使开发专门针对预防这些分子事件的治疗方法。除了单基因疾病外，患有结构性心脏病的患者因遗传的DNA多态性而易患心房颤动。在未来几年内，通过开发具有数十万个单核苷酸多态性的芯片进行全基因组扫描，将阐明易患心房颤动的单核苷酸多态性。在未来十年内，可能会鉴定出大多数导致心房颤动的基因以及赋予易感性的单核苷酸多态性，并将根据个体的基因组概况开发治疗方法。在这篇综述中，我概述了目前已鉴定出的相关基因突变的认识，并简要讨论了这些信息可能对临床实践产生的影响。
