Gene-guided therapy for catheter-ablation of atrial fibrillation: are we there yet?

Excerpt

In the last decade, increasing evidence has emerged for a genetic predisposition to atrial fibrillation (AF). In 2003, Mayo Clinic investigators showed that 15 % of patients with lone AF had a positive family history of the condition [1]. Subsequent epidemiological studies observed that the odds of developing AF increased three to five-fold depending on the age of onset of AF in a parent [2, 3]. Furthermore, numerous genes associated with AF have been identified using positional cloning and linkage analyses, candidate gene and exome-sequencing approaches [4]. In 2003, the first gene (KCNQ1) encoding the delayed cardiac rectifier potassium channel (I_Ks) was linked with familial AF. [5] Mutations encoding cardiac ion channels (Na⁺, K⁺ and Ca²⁺), gap junction proteins (connexins) and signaling molecules (nucleoporin 155 [NUP155], natriuretic peptide precursor A [NPPA]) have been described in Mendelian forms of AF. However, the extent to which genetic factors contribute to the more common forms of AF remained unclear until the advent of genome-wide association studies (GWAS). …