Familial atrial fibrillation is a genetically heterogeneous disorder

Dawood Darbar, Kathleen J. Herron, Jeffrey D. Ballew, Arshad Jahangir, Bernard J. Gersh, Win K. Shen, Stephen C. Hammill, Douglas L. Packer, Timothy M. Olson

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

OBJECTIVES: The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous. BACKGROUND: Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10. METHODS: Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus. RESULTS: Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 ± 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy. CONCLUSIONS: Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.

Original languageEnglish (US)
Pages (from-to)2185-2192
Number of pages8
JournalJournal of the American College of Cardiology
Volume41
Issue number12
DOIs
StatePublished - Jun 18 2003

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Darbar, D., Herron, K. J., Ballew, J. D., Jahangir, A., Gersh, B. J., Shen, W. K., Hammill, S. C., Packer, D. L., & Olson, T. M. (2003). Familial atrial fibrillation is a genetically heterogeneous disorder. Journal of the American College of Cardiology, 41(12), 2185-2192. https://doi.org/10.1016/S0735-1097(03)00465-0