Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence

• Published in: PloS one Vol. 2; no. 10; p. e1051
• Main Authors: Mohler, Peter J, Healy, Jane A, Xue, Hui, Puca, Annibale A, Kline, Crystal F, Allingham, R Rand, Kranias, Evangelia G, Rockman, Howard A, Bennett, Vann
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-10-2007; Public Library of Science (PLoS)
• Subjects: Aging; Animals; Ankyrins; Ankyrins - genetics; Ankyrins - physiology; Arrhythmia; Biochemistry; Biochemistry/Cell Signaling and Trafficking Structures; Biophysics; Cardiac arrhythmia; Cardiomyocytes; Cardiovascular Disorders/Arrhythmias, Electrophysiology, and Pacing; Cellular Senescence; Death; Echocardiography - methods; Genetics and Genomics/Disease Models; Heart; Heart diseases; Heart Diseases - genetics; Heart Diseases - pathology; Homeostasis; Humans; Internal medicine; Life span; Medicine; Mice; Mice, Inbred C57BL; Muscle contraction; Mutation; Myocardial Contraction; Phenotype; Physiology; Potassium; Proteins; Risk; Risk factors; Rodents; Senescence; Sodium; Syndrome; North Carolina; Italy; Iowa City Iowa; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001051

Here we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants. The prevalence of certain ANK2 (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and in vitro phenotypes were unexpectedly common. Studies with the ankyrin-B(+/-) mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term "ankyrin-B syndrome", which may contribute to both aging-related disorders and enhanced cardiac function.