ArticleCirculation. Cardiovascular genetics2014
Pitx2, an atrial fibrillation predisposition gene, directly regulates ion transport and intercalated disc genes.
Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 6 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 6 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- The Role of Genetics in Stroke Risk and Outcome: A Review of Current Evidence.Brain and behavior · 2025Pooled it
- Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation.Nature communications · 2025Pooled it
- A Network and Pathway Analysis of Genes Associated With Atrial Fibrillation.Cardiovascular therapeutics · 2024Pooled it
- Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.Circulation. Genomic and precision medicine · 2020Pooled it
- Association between gene variants and the recurrence of atrial fibrillation: An updated meta-analysis.Medicine · 2019Pooled it
- Common genetic variants and response to atrial fibrillation ablation.Circulation. Arrhythmia and electrophysiology · 2015Pooled it
- PITX2C deficiency promotes arrhythmogenic remodelling via oxidative stress in atrial myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Mass spectrometric proteome profiling using a deep spectral library reveals homogenization of right and left atrial proteomes in persistent atrial fibrillation patients.Cardiovascular research · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Transcriptomic Landscape of Human Left and Right Atria Associated with Atrial Fibrillation.Anatolian journal of cardiology · 2025Article
- Atrial Fibrillation Begets Atrial Fibrillation in Small Animals: Characterization of New Rat Model of Spontaneous Atrial Fibrillation.Biomedicines · 2025Article
- Oxidative Stress Causes Mitochondrial and Electrophysiologic Dysfunction to Promote Atrial Fibrillation inCirculation. Arrhythmia and electrophysiology · 2025Article
- Transgenic mice overexpressing Pitx2 in the atria develop tachycardia-bradycardia syndrome.PloS one · 2025Article
- Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy.Nature genetics · 2024Article
- Transient titin-dependent ventricular defects during development lead to adult atrial arrhythmia and impaired contractility.iScience · 2024Article
- Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.JACC. Basic to translational science · 2024Review
- A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.Circulation · 2024Article
- Atrial fibrillation: pathophysiology, genetic and epigenetic mechanisms.The Lancet regional health. Europe · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation (AF) locus. When deleted in the mouse germline, Pitx2 haploinsufficiency predisposes to pacing-induced AF, indicating that reduced Pitx2 promotes an arrhythmogenic substrate. Previous work focused on Pitx2 developmental functions that predispose to AF. Although Pitx2 is expressed in postnatal left atrium, it is unknown whether Pitx2 has distinct postnatal and developmental functions. METHODS AND
resultsTo investigate Pitx2 postnatal function, we conditionally inactivated Pitx2 in the postnatal atrium while leaving its developmental function intact. Unstressed adult Pitx2 homozygous mutant mice display variable R-R interval with diminished P-wave amplitude characteristic of sinus node dysfunction, an AF risk factor in human patients. An integrated genomics approach in the adult heart revealed Pitx2 target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators. Importantly, many Pitx2 target genes have been implicated in human AF by genome-wide association studies. Immunofluorescence and transmission electron microscopy studies in adult Pitx2 mutant mice revealed structural remodeling of the intercalated disc characteristic of human patients with AF.
conclusionsOur findings, revealing that Pitx2 has genetically separable postnatal and developmental functions, unveil direct Pitx2 target genes that include channel and calcium handling genes, as well as genes that stabilize the intercalated disc in postnatal atrium.
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