Genetic variation is an important determinant of atrial fibrillation (AF) susceptibility.
Numerous rare variants in protein-coding sequences of genes have been associated with
AF in families and in early-onset cases, and chromosomal loci harbouring common risk
variants have been mapped in AF cohorts. Many of these loci are in non-coding regions
of the human genome and are thought to contain regulatory sequences that modulate
gene expression. Disease genes implicated to date have predominantly encoded cardiac
ion channels, with predicted mutation effects on the atrial action potential duration.
More recent studies have expanded the spectrum of disease-associated genes to include
myocardial structural components and have highlighted an unsuspected role for cardiac
transcription factors. These paradigm-shifting discoveries suggest that abnormalities
of atrial specification arising during cardiac development might provide a template
for AF in later adult life. With the escalating pace of variant discovery, there is
an increasing need for mechanistic studies not only to evaluate single variants, but
also to determine the collective effects of each person’s burden of rare and common
genetic variants, co-morbidities and lifestyle factors on the atrial substrate for
arrhythmogenesis. Elucidation of an individual’s genetic predisposition and modifiable
environmental risk factors will facilitate personalised approaches to AF treatment.
Keywords
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Article info
Publication history
Published online: May 11, 2017
Identification
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© 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
