PITX2 defiency identifies changes in sarcomere structure and mitochondrial dysfunktion as substrates for atrial fibrillation

Atrial fibrillation affects 2-3% of the population and is associated with high morbidity and mortality from cardiovascular causes in patients. Common gene variants on chromosome 4q25 show the strongest genomic disease association and reside in an enhancer region regulating the Paired like Homeodomain 2 (PITX2) gene. Mechanisms how PITX2 is linked with AF remains unknown. Differences in protein abundance was compared in PITX2 knockout human induced pluripotent stem cell-derived atrial cardiomyocytes and their respective isogenic controls from six independent differentiation runs.