Genetics of atrial fibrillation

Abstract

Recent studies of atrial fibrillation (AF) have identified mutations in a series of ion channels; however, these mutations appear to be relatively rare causes of AF. A genome-wide association study has identified novel variants on chromosome 4 associated with AF, although the mechanism of action for these variants remains unknown. Ultimately, a greater understanding of the genetics of AF should yield insights into novel pathways, therapeutic targets, and diagnostic testing for this common arrhythmia.

Figure 1

Both gain of function and loss of function mutations in I_Ks have been associated with AF. Mutations in KCNQ1 and KCNE2 increase the current I_Ks, which is predicted to shorten the action potential (dashed line) in cardiac myocytes and render atrial myocytes susceptible to reentrant arrhythmias. Mutations in KCNA5 (Kv1.5) that are predicted to prolong the action potential duration (dotted line) have also been associated with AF.