Atrial fibrillation--a new cardiac channelopathy

Abstract

Atrial fibrillation (AF) is a common complication of a wide range of cardiac and systemic diseases and is regarded generally as a sporadic, acquired disorder. Familial clustering of AF has been reported but definitive links of genetic factors with AF pathogenesis have been lacking. Genome-wide linkage studies and the discovery of mutations in families with AF have provided compelling evidence that genetic factors can have a role in the development of AF. Although relatively few disease genes have been identified, current data indicate that inherited defects in cardiac ion channel genes can predispose to AF by altering ion channel activation and atrial conduction properties. Mutations in the reported disease genes account for only a minority of all familial AF cases and further gene discovery studies are required. Characterisation of the genetic variants that cause AF in families provides a framework for elucidation of key disease pathways that underlie the more commonly-occurring complex forms of AF. A better understanding of the molecular and electrophysiological defects that promote AF in families and in the general population will facilitate new approaches to the diagnosis, prevention and treatment of AF.