ArticleBasic research in cardiology2016
Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation.
Article in Basic research in cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Article
- Linking shox/shox2 deficiency with fgfr3 gain-of-function and natriuretic peptides.Frontiers in endocrinology · 2026Article
- Discovery ofDiagnostics (Basel, Switzerland) · 2025Article
- The Neglected Internodal Tract-A Cardiac Conduction System Structure Homologous to the Development and Regulation of the Sinoatrial Node.Reviews in cardiovascular medicine · 2025Review
- Inflammation pathways as therapeutic targets in angiotensin II induced atrial fibrillation.Frontiers in pharmacology · 2025Review
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Genetic and non-genetic risk factors associated with atrial fibrillation.Life sciences · 2022Review
- Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.Journal of cardiovascular development and disease · 2022Review
- A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus.Genetics and molecular biology · 2022Article
- PRRX1 Loss-of-Function Mutations Underlying Familial Atrial Fibrillation.Journal of the American Heart Association · 2021Article
- A narrative review of non-coding RNAs in atrial fibrillation: potential therapeutic targets and molecular mechanisms.Annals of translational medicine · 2021Review
- Transcriptional factors in calcium mishandling and atrial fibrillation development.Pflugers Archiv : European journal of physiology · 2021Review
- The Transcription Factor Shox2 Shapes Neuron Firing Properties and Suppresses Seizures by Regulation of Key Ion Channels in Thalamocortical Neurons.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Atrial and Sinoatrial Node Development in the Zebrafish Heart.Journal of cardiovascular development and disease · 2021Review
- Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach.Proteomes · 2021Review
- Genetic Complexity of Sinoatrial Node Dysfunction.Frontiers in genetics · 2021Review
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia with a strong genetic component. Molecular pathways involving the homeodomain transcription factor Shox2 control the development and function of the cardiac conduction system in mouse and zebrafish. Here we report the analysis of human SHOX2 as a potential susceptibility gene for early-onset AF. To identify causal variants and define the underlying mechanisms, results from 378 patients with early-onset AF before the age of 60 years were analyzed and compared to 1870 controls or reference datasets. We identified two missense mutations (p.G81E, p.H283Q), that were predicted as damaging. Transactivation studies using SHOX2 targets and phenotypic rescue experiments in zebrafish demonstrated that the p.H283Q mutation severely affects SHOX2 pacemaker function. We also demonstrate an association between a 3'UTR variant c.*28T>C of SHOX2 and AF (p = 0.00515). Patients carrying this variant present significantly longer PR intervals. Mechanistically, this variant creates a functional binding site for hsa-miR-92b-5p. Circulating hsa-miR-92b-5p plasma levels were significantly altered in AF patients carrying the 3'UTR variant (p = 0.0095). Finally, we demonstrate significantly reduced SHOX2 expression levels in right atrial appendages of AF patients compared to patients with sinus rhythm. Together, these results suggest a genetic contribution of SHOX2 in early-onset AF.
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