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.

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改变心房颤动免疫反应的遗传因素：JACC 本周评论主题

心房颤动 (AF) 是全世界最常见的心律失常，与一系列不良临床结果相关。越来越多的证据表明先天免疫反应引起的炎症过程是房颤发病机制的基石。影响白细胞的遗传和表观遗传因素已被确定为炎症反应的关键调节因子。编码参与先天免疫反应的蛋白质的基因的遗传变异与房颤患者房颤复发和中风的风险增加有关。此外，与不确定潜力的克隆造血、白细胞端粒缩短和表观遗传年龄加速相关的获得性体细胞突变导致房颤风险增加。在具有不确定潜力的克隆造血功能的个体中，心肌单核细胞来源的巨噬细胞向促炎表型转变可能会引发房颤。需要进一步的研究来更好地了解天然免疫反应的基因调控在房性心律失常发生中的作用及其作为个性化医疗目标的治疗潜力。