Cardiac-specific expression of the N1325S mutation of SCN5A in transgenic mouse hearts (TG-NS) resulted in long QT syndrome (LQTS), ventricular arrhythmias (VT), and heart failure. In this study we carried out oligonucleotide mircoarray analysis to identify genes that are differentially expressed in the TG-NS mouse hearts. We identified 33 genes in five different functional groups that showed differential expression. None of the 33 genes are ion channel genes. STAT1, which encodes a transcription factor involved in apoptosis and interferon response, showed the most significant difference of expression between TG-NS and control mice (a nearly 10-fold increase in expression, P = 4 x 10(-6)). The results were further confirmed by quantitative real-time PCR and Western blot analyses. Accordingly, many interferon response genes also showed differential expression in TG-NS hearts. This study represents the first microarray analysis for LQTS and implicates STAT1 in the pathogenesis and progression of LQTS and heart failure. (C) 2007 Elsevier Inc. All rights reserved.