Locus for atrial fibrillation maps to chromosome 6q14-6
Locus for atrial fibrillation maps to chromosome 6q14-6
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DOI：
10.1161/01.cir.0000077910.80718.49
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发表时间：
2003-06-17
期刊：
影响因子：
37.8
通讯作者：
MacRae, CA
中科院分区：
文献类型：
--
作者：
Ellinor, PT;Shin, JT;MacRae, CA
心房颤动（AF）是临床上最常见的心律失常，是导致发病和死亡的主要原因。虽然AF通常与其他心血管疾病相关，但许多患者没有明显的病因。存在遗传形式的AF，但致病基因仅在单个家族中被定义。我们已经确定了一个大的家庭（家庭FAF-1），其中AF分离为孟德尔trait.Methods和结果34个家庭成员进行了评估，12导联心电图，超声心动图，24小时霍尔特监测，和实验室研究。有心电图记录的房颤患者被定义为受影响。如果受试者年龄>60岁，没有AF个人病史，并且没有AF病史的后代，则认为受试者未受影响。提取DNA并使用多态性微卫星标记进行基因型分析。在6号染色体上获得了连锁的证据，在标记D 6S 1021处的优势（LOD）得分的峰值2点对数为3.63（θ =0）。在D 6S 286和D 6S 1021之间获得的最大多点LOD得分为4.9，表明该区间作为该家族中AF的基因缺陷位置的优势接近100000：1。LOD评分对等位基因频率和等位基因频率的变化具有鲁棒性。单倍型分析进一步支持这一最小的遗传interval. Conclusion，我们已经映射到染色体6 q14 -16的一个新的基因座AF。在此期间致病基因的鉴定将是理解AF基本机制的重要一步。
Background-Atrial fibrillation (AF), the most common clinical arrhythmia, is a major cause of morbidity and mortality. Although AF is often associated with other cardiovascular conditions, many patients present without an obvious etiology. Inherited forms of AF exist, but the causative gene has been defined only in a single family. We have identified a large family (family FAF-1) in which AF segregates as a Mendelian trait.Methods and Results-Thirty-four family members were evaluated by 12-lead ECG, echocardiogram, 24-hour Holter monitoring, and laboratory studies. Individuals with electrocardiographically documented AF were defined as affected. Subjects were considered unaffected if they were >60 years of age, had no personal history of AF, and had no offspring with a history of AF. DNA was extracted and genotypic analyses were performed using polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 6, with a peak 2-point logarithm of the odds (LOD) score of 3.63 (theta=0) at the marker D6S1021. A maximal multipoint LOD score of 4.9 was obtained between D6S286 and D6S1021, indicating odds of approximate to100 000:1 in favor of this interval as the location of the gene defect responsible for AF in this family. The LOD scores were robust to changes in penetrance and allele frequency. Haplotype analyses further supported this minimal genetic interval.Conclusion-We have mapped a novel locus for AF to chromosome 6q14-16. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of AF.