Genetic factors contribute substantially to atrial fibrillation susceptibility through mutations in ion channels, structural proteins, transcriptional regulators, and calcium-handling proteins.
This review outlines the genetic basis of atrial fibrillation across four functional modules to provide a framework for precision medicine approaches in cardiac electrophysiology.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by rapid and disorganized electrical activity in the atria. Although traditionally attributed to aging and structural remodeling secondary to cardiovascular comorbidities, AF has a well-recognized heritable component, with genetic factors contributing substantially to disease susceptibility. This review systematically evaluates the molecular landscape of AF, focusing on genetic mutations and their functional consequences in disease development. AF-associated genes are organized into four functional modules: (1) ion channelopathies (SCN5A, KCNQ1, KCNH2, KCNA5); (2) structural myopathies (TTN, MYL4, GJA5, COL1A1); (3) transcriptional regulators (PITX2, GATA4, TBX5, NKX2-5, GATA6, ZFHX3); and (4) calcium handling proteins (RYR2, CASQ2, JPH2, ANKB, PLN, TRDN). For each gene, population prevalence and penetrance of associated variants are discussed alongside the specific molecular and biophysical consequences of causative mutations. By elucidating how these protein alterations converge on shared electrophysiological and structural substrates, we provide a framework for transitioning from generalized therapeutic strategies to precision medicine approaches in cardiac electrophysiology.
Hinge et al. (Fri,) conducted a review in Atrial Fibrillation. Genetic factors contribute substantially to atrial fibrillation susceptibility through mutations in ion channels, structural proteins, transcriptional regulators, and calcium-handling proteins.