{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T15:28:06Z","timestamp":1744298886823,"version":"3.37.3"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OCI\u20101124123"],"award-info":[{"award-number":["OCI\u20101124123"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associates with corrected QT interval (QTc) prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associated with congenital and acquired health conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis.<\/jats:title><jats:p>DNA microsatellite polymorphism may associate with QTc response to dofetilide initiation in patients with persistent AF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed whole\u2010exome sequencing in a cohort of patients with persistent AF undergoing DI. Electrocardiographic variables and clinical data were assessed. We defined patients as eligible for DI when no significant QTc prolongation (&gt;20% compared with baseline) was seen with a 500\u2010\u03bcg dose. We defined patients as ineligible for DI when significant QTc prolongation was seen during DI with 500\u2009\u03bcg. We investigated polymorphisms for 11\u2009919 DNA microsatellite loci in relation to QTc response to DI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the study, 14 consecutive patients with persistent AF presenting for DI were enrolled. Whole\u2010exome sequencing revealed 14 different microsatellite loci in the 2 groups. All genes or proximal genes that harbor these loci are known to have expression in the human heart. Two genes, <jats:italic>MYH6<\/jats:italic> and <jats:italic>TRAK2<\/jats:italic>, are known to have expression in the atria. <jats:italic>TRAK2<\/jats:italic> is known to interact with KCNJ2, the inward\u2010rectifier potassium channel 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Microsatellite DNA polymorphisms seem to associate with QTc response to DI therapy in patients with persistent AF who are deemed otherwise eligible for dofetilide therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.22969","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T15:13:20Z","timestamp":1524150800000},"page":"849-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole\u2010exome sequencing reveals microsatellite DNA markers for response to dofetilide initiation in patients with persistent atrial fibrillation: A pilot study"],"prefix":"10.1002","volume":"41","author":[{"given":"Nick","family":"Kinney","sequence":"first","affiliation":[{"name":"Edward Via College of Osteopathic Medicine  Blacksburg Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Carilion Clinic and Virginia Tech Carilion School of Medicine  Roanoke Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Kim","sequence":"additional","affiliation":[{"name":"Carilion Clinic and Virginia Tech Carilion School of Medicine  Roanoke Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6244-8220","authenticated-orcid":false,"given":"Robin T.","family":"Varghese","sequence":"additional","affiliation":[{"name":"Edward Via College of Osteopathic Medicine  Blacksburg 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