HCN4 Gene Polymorphisms Are Associated With Occurrence of Tachycardia-Induced Cardiomyopathy in Patients With Atrial Fibrillation

Tachycardia-induced cardiomyopathy (TIC) is a reversible cardiomyopathy induced by tachyarrhythmia, and the genetic background of the TIC is not well understood. The hyperpolarization-activated cyclic nucleotide-gated channel gene is highly expressed in the conduction system where it is involved in heart rate control. We speculated that the gene is associated with TIC. We enrolled 930 Japanese patients with atrial fibrillation (AF) for screening, 350 Japanese patients with AF for replication, and 1635 non-AF controls. In the screening AF set, we compared single-nucleotide polymorphism genotypes between AF subjects with TIC (TIC, n=73) and without TIC (non-TIC, n=857). Of 17 gene-tag single-nucleotide polymorphisms, rs7172796, rs2680344, rs7164883, rs11631816, and rs12905211 were significantly associated with TIC. Among them, only rs7164883 was independently associated with TIC after conditional analysis (TIC versus non-TIC: minor allele frequency, 26.0% versus 9.7%; =1.62×10 ; odds ratio=3.2). We confirmed this association of single-nucleotide polymorphism rs7164883 with TIC in the replication set (TIC=41 and non-TIC=309; minor allele frequency, 28% versus 9.9%; =1.94×10 ; odds ratio=3.6). The minor allele frequency of rs7164883 was similar in patients with AF and non-AF controls (11% versus 10.9%; =0.908). The gene single-nucleotide polymorphism rs7164883 may be a new genetic marker for TIC in patients with AF.