Inherited genetic variants and acquired somatic mutations, such as clonal hematopoiesis, modulate innate immune responses and are associated with increased risk of atrial fibrillation and stroke.
How do genetic and epigenetic factors altering the innate immune response affect the risk and outcomes of atrial fibrillation?
Genetic and epigenetic modulation of the innate immune system plays a key role in atrial fibrillation pathogenesis, offering potential targets for personalized medicine.
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and is associated with a range of adverse clinical outcomes. Accumulating evidence points to inflammatory processes resulting from innate immune responses as a cornerstone in AF pathogenesis. Genetic and epigenetic factors affecting leukocytes have been identified as key modulators of the inflammatory response. Inherited variants in genes encoding proteins involved in the innate immune response have been associated with increased risk for AF recurrence and stroke in AF patients. Furthermore, acquired somatic mutations associated with clonal hematopoiesis of indeterminate potential, leukocyte telomere shortening, and epigenetic age acceleration contribute to increased AF risk. In individuals carrying clonal hematopoiesis of indeterminate potential, myocardial monocyte-derived macrophage shift toward a proinflammatory phenotype may precipitate AF. Further studies are needed to better understand the role of genetic regulation of the native immune response in atrial arrhythmogenesis and its therapeutic potential as a target for personalized medicine.
Ninni et al. (Fri,) conducted a review in Atrial fibrillation. Inherited genetic variants and acquired somatic mutations, such as clonal hematopoiesis, modulate innate immune responses and are associated with increased risk of atrial fibrillation and stroke.