Somatic mutations and atrial fibrillation: the end or just the beginning?

Abstract

Atrial fibrillation (AF) is a common, morbid, and heritable arrhythmia. Well-documented Mendelian1 and polygenic2 contributions to the inherited basis for AF exist. In contrast, the potential contribution of somatic or acquired mutations in atrial tissue has not been extensively explored for AF. The hypothesis that somatic mutations may underlie AF is particularly intriguing when considering that AF is largely a tissue-specific disease (albeit influenced by systemic modulating factors such as inflammation or autonomic tone). Thus, it stands to reason that mutations specific to atrial or pulmonary venous tissue might be sufficient to initiate the complex cascade of molecular events leading to AF. Article see p 50 In 2006, Gollob et al3 reported that somatic mutations in GJA5 , a gene encoding a cardiac gap junction protein, connexin 40, were found in cardiac tissue from 3 of 15 patients with idiopathic AF who had undergone surgical AF ablation. This observation supported the notion that somatic mutations might underlie a substantial proportion of AF. In a subsequent report, a mutation was identified in GJA1 or connexin 43, which again supported somatic mosaicism as a mechanism of AF.4 In this issue of Circulation Cardiovascular …