Molecular genetics of atrial fibrillation

Chia Ti Tsai, Ling Ping Lai, Jiunn Lee Lin, Fu Tien Chiang

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. There is genetic predisposition for the development of AF. Recently, by linkage analysis, several loci have been mapped for monogenetic AF, which include 11p15.5, 21q22, 17q, 7q35-36, 5p13, 6q14-16, and 10q22. Some of these loci encode for subunits of potassium channels (KCNQ1, KCNE2, KCNJ2 and KCNH2 genes), and the remaining are yet unidentified. All of the mutations are associated with a gain of function of repolarization potassium currents, resulting in a shortening of action potential duration and atrial refractory period, which facilitate multiple reentrant circuits in AF. In addition to familial AF, common AF often occurs in association with acquired diseases such as hypertension, valvular heart disease, or heart failure. By genetic association study, some genetic variants or polymorphisms related to the mechanism of AF have been found to be associated with common AF, including genes encoding for subunits of potassium or sodium channels, sarcolipin, renin-angiotensin-aldosterone system genes, connexin 40 gene, endothelial nitric oxide synthase gene, and interleukin 10 genes. These observations suggest that genes related to ionic channels, calcium-handling protein, fibrosis, conduction and inflammation play important roles in the pathogenesis of common AF. The complete elucidation of genetic loci for common AF is still in its infancy. However, the availability of genome-wide scans with hundreds or thousands of polymorphisms will, in the future, make it possible. However, challenges and pitfalls exist in association studies, and consideration of particular features of study design is necessary before making definite conclusions from these studies.

Original languageEnglish
Pages (from-to)177-190
Number of pages14
JournalActa Cardiologica Sinica
Volume24
Issue number4
Publication statusPublished - Dec 1 2008
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Familial
  • Genetics
  • Multifactorial

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Tsai, C. T., Lai, L. P., Lin, J. L., & Chiang, F. T. (2008). Molecular genetics of atrial fibrillation. Acta Cardiologica Sinica, 24(4), 177-190.