Entius M M, Groenewegen A, Pronk A, van der Smagt J J, Loh P, Hauer R N, Derksen R, van Gelder I C, Lok D J A, Doevendans P A
Neth Heart J. 2005 Aug;13(7-8):269-273.
Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterised by rapid and irregular contraction of the atrium. The risk of AF increases with age and AF increases the risk of various heart disorders, stroke and mortality. AF can occur in a sporadic or familial form. The underlying mechanism leading to AF is not well known but genetic analysis can increase our insight into the molecular pathways in AF. Detailed information on the molecular mechanisms of a disorder increase options for diagnosis and treatment. Recently, a gain-of-function mutation in exon of the KCNQ1 gene located on chromosome 11 was identified in a large Chinese AF family. KCNQ1 associates with KCNE1 or KCNE2 (both located on chromosome 21) to form cardiac potassium channels. Subsequent analysis of Chinese families showed a KCNE2 mutation in two families. Other genetic studies show linkage to chromosome 6 and 10, indicating genetic heterogeneity. A number of studies have shown that altered expression of the atrial connexin40 protein is a risk factor for AF. Connexin genes encode gap-junction proteins that are important in cardiac conduction and for normal wave propagation.
OBJECTIVES/METHODS: In this study we analysed the role of KCNQ1, KCNE1 coding region and Cx40 promoter region in six Dutch AF families by sequence analysis.
No mutations were found in these genes. The absence of mutations indicates genetic heterogeneity in familial AF; however, further research is needed. Candidate genes are being sequenced, linkage analysis in a large family will be performed and additional AF families will be collected.
心房颤动（AF）是最常见的心律失常，其特征为心房快速且不规则收缩。AF的风险随年龄增长而增加，并且AF会增加各种心脏疾病、中风和死亡的风险。AF可呈散发性或家族性形式出现。导致AF的潜在机制尚不清楚，但基因分析可增进我们对AF分子途径的了解。关于一种疾病分子机制的详细信息可增加诊断和治疗的选择。最近，在一个大型中国AF家族中，发现位于11号染色体上的KCNQ1基因外显子存在功能获得性突变。KCNQ1与KCNE1或KCNE2（均位于21号染色体上）结合形成心脏钾通道。对中国家族的后续分析显示，有两个家族存在KCNE2突变。其他基因研究表明与6号和10号染色体存在连锁关系，提示存在遗传异质性。多项研究表明，心房连接蛋白40（Cx40）的表达改变是AF的一个风险因素。连接蛋白基因编码在心脏传导和正常电波传播中起重要作用的间隙连接蛋白。
目的/方法：在本研究中，我们通过序列分析，对六个荷兰AF家族中的KCNQ1、KCNE1编码区和Cx40启动子区的作用进行了分析。
在这些基因中未发现突变。未发现突变表明家族性AF存在遗传异质性；然而，仍需要进一步研究。正在对候选基因进行测序，将在一个大型家族中进行连锁分析，并将收集更多的AF家族。
