Common Variants in KCNN3 are Associated with Lone Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia. A subset of patients with lone AF have no overt heart disease and an increased heritability of AF. We sought to identify common genetic variants underlying lone AF. Cases were from the German AF Network, Heart and Vascular Health Stud...

Descripción completa

Detalles Bibliográficos
Autores principales: Ellinor, Patrick T., Lunetta, Kathryn L., Glazer, Nicole L., Pfeufer, Arne, Alonso, Alvaro, Chung, Mina K., Sinner, Moritz F., de Bakker, Paul I. W., Mueller, Martina, Lubitz, Steven A., Fox, Ervin, Darbar, Dawood, Smith, Nicholas L., Smith, Jonathan D., Schnabel, Renate B., Soliman, Elsayed Z., Rice, Kenneth M., Van Wagoner, David R., Beckmann, Britt-M., van Noord, Charlotte, Wang, Ke, Ehret, Georg B., Rotter, Jerome I., Hazen, Stanley L., Steinbeck, Gerhard, Smith, Albert V., Launer, Lenore J., Harris, Tamara B., Makino, Seiko, Nelis, Mari, Milan, David J., Perz, Siegfried, Esko, Tõnu, Köttgen, Anna, Moebus, Susanne, Newton-Cheh, Christopher, Li, Man, Möhlenkamp, Stefan, Wang, Thomas J., Kao, W.H. Linda, Vasan, Ramachandran S., Nöthen, Markus M., MacRae, Calum A., Stricker, Bruno H. Ch., Hofman, Albert, Uitterlinden, André G., Levy, Daniel, Boerwinkle, Eric, Metspalu, Andres, Topol, Eric J., Chakravarti, Aravinda, Gudnason, Vilmundur, Psaty, Bruce M., Roden, Dan M., Meitinger, Thomas, Wichmann, H.-Erich, Witteman, Jacqueline C.M., Barnard, John, Arking, Dan E., Benjamin, Emelia J., Heckbert, Susan R., Kääb, Stefan
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871387/
https://www.ncbi.nlm.nih.gov/pubmed/20173747
http://dx.doi.org/10.1038/ng.537
Descripción
Sumario:Atrial fibrillation (AF) is the most common sustained arrhythmia. A subset of patients with lone AF have no overt heart disease and an increased heritability of AF. We sought to identify common genetic variants underlying lone AF. Cases were from the German AF Network, Heart and Vascular Health Study, Atherosclerosis Risk in Communities Study, Cleveland Clinic, and Massachusetts General Hospital. Subjects were genotyped, HapMap SNPs imputed, and age- sex- and hypertension-adjusted analyses performed. A meta-analysis was conducted using 1,335 cases of lone AF and 12,844 referents. A novel locus on chromosome 1q21 was identified, and the most significant SNP, rs13376333, had an adjusted odds ratio of 1.56 (P=6.3×10(−12)). This association was replicated in two cohorts with lone AF for an overall odds ratio of 1.52 (P=1.83×10(−21)). Rs13376333 is intronic to KCNN3, a potassium channel involved in atrial repolarization. KCNN3 represents a novel potential therapeutic target in the treatment of AF.

Ejemplares similares