Locus for atrial fibrillation maps to chromosome 6q14-16.

Abstract:

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 approximately 100 000:1 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. CONCLUSIONS: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.

journal_name

Circulation

journal_title

Circulation

authors

Ellinor PT,Shin JT,Moore RK,Yoerger DM,MacRae CA

doi

10.1161/01.CIR.0000077910.80718.49

subject

Has Abstract

pub_date

2003-06-17 00:00:00

pages

2880-3

issue

23

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000077910.80718.49

journal_volume

107

pub_type

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