Minor allele of GJA1 gene polymorphism is associated with higher heart rate during atrial fibrillation

• Published in: Scientific reports Vol. 11; no. 1; p. 2549
• Main Authors: Okamura, Sho, Onohara, Yuko, Ochi, Hidenori, Tokuyama, Takehito, Hironobe, Naoya, Okubo, Yosaku, Ikeuchi, Yoshihiro, Miyauchi, Shunsuke, Chayama, Kazuaki, Kihara, Yasuki, Nakano, Yukiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-01-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308; 692/4019; Ablation; Alleles; Cardiac arrhythmia; Conduction; Congestive heart failure; Connexin 43; Electrophysiological recording; Fibrillation; Gap junctions; Gene polymorphism; Genetic markers; Genome-wide association studies; Genomes; Heart rate; Humanities and Social Sciences; multidisciplinary; Multivariate analysis; Replication; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Tachycardia; Ventricle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-82117-3

Atrial fibrillation (AF) tachycardia causes heart failure and requires more attention. The genetic background of individual heart rate (HR) variations during AF are unclear. We hypothesized that HR-associated single nucleotide polymorphisms (SNPs) reported in Genome-Wide Association Studies (GWAS) are also associated with HR during AF. We enrolled patients with persistent AF (311 for screening and 146 for replication) who underwent AF ablation and were genotyped for the 21 h-associated SNPs reported in GWAS. The patients underwent 24-h Holter monitoring before AF ablation and electrophysiological study after AF ablation during sinus rhythm. Only the
GJA1
SNP rs1015451 (T>C) was significantly associated with total HR (TT 110,643 ± 17,542 beats/day, TC 116,350 ± 19,060 beats/day, CC 122,163 ± 25,684 beats/day,
P
 = 8.5 × 10
−4
). We also confirmed this significant association in the replication set. The intra-atrial conduction was faster in AF patients with the
GJA1
minor allele than in those without it. Multivariate analysis revealed the presence of a
GJA1
SNP rs1015451 additive model, female gender, lower left ventricular ejection fraction, and higher 1:1 atrioventricular nodal conduction were independently associated with higher HR during AF. The
GJA1
SNP might be a new genetic marker for AF tachycardia.