Department of Cardiovascular Medicine, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Health Management, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan; Department of Gastroenterology and Metabolism, Biomedical Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Heart Rhythm. 2022 Dec;19(12):2044-2050. doi: 10.1016/j.hrthm.2022.08.024. Epub 2022 Aug 28.
Atrial fibrillation (AF) and recurrence of AF after pulmonary vein isolation (PVI) have been linked to sinus node dysfunction.
The purpose of this study was to investigate the association between the heart rate-associated single nucleotide polymorphisms (SNPs) identified in genome-wide association studies and recurrence of AF after PVI.
In this study, patients with paroxysmal AF who underwent initial PVI, including 522 patients for screening and 172 patients for replication, were recruited and 21 heart rate-associated SNPs identified in genome-wide association studies were genotyped. The association between these SNPs and the recurrence of AF was investigated.
Throughout the follow-up period of 21 ± 12 months, 119 patients with paroxysmal AF (22.8%) exhibited AF recurrences in the screening set. The rate of AF recurrence was significantly associated with the minor allele C of the gap junction alpha-1 protein (GJA1) rs1015451 (additive model: odds ratio 2.07; P = 9.32 × 10), but not with other SNPs. This association was confirmed in the replication set (allelic model: odds ratio 1.81; P = 2.70 × 10). Multivariate analysis revealed that the recurrence of AF after AF ablation was independently related to the GJA1 SNP rs1015451 additive model, duration of AF >1 year, AF from non-pulmonary vein foci, and thicker interventricular septum.
The GJA1 SNP rs1015451, coding for a gap junction protein (connexin-43), may be considered a novel genetic marker for AF recurrence after PVI.
心房颤动（AF）和肺静脉隔离（PVI）后 AF 的复发与窦房结功能障碍有关。
本研究旨在探讨全基因组关联研究中鉴定的与心率相关的单核苷酸多态性（SNP）与 PVI 后 AF 复发之间的关系。
本研究纳入了接受初始 PVI 的阵发性 AF 患者，包括 522 例用于筛查和 172 例用于复制的患者，并对 21 个全基因组关联研究中鉴定的与心率相关的 SNP 进行了基因分型。研究了这些 SNP 与 AF 复发之间的关系。
在 21±12 个月的随访期间，筛查组中 119 例阵发性 AF 患者（22.8%）出现 AF 复发。AF 复发的发生率与缝隙连接蛋白 alpha-1 （GJA1）rs1015451 的次要等位基因 C（加性模型：优势比 2.07；P=9.32×10）显著相关，但与其他 SNP 无关。该关联在复制组中得到了证实（等位基因模型：优势比 1.81；P=2.70×10）。多变量分析显示，AF 消融后 AF 的复发与 GJA1 SNP rs1015451 的加性模型、AF 持续时间>1 年、非肺静脉病灶起源的 AF 和间隔较厚独立相关。
编码缝隙连接蛋白（连接蛋白-43）的 GJA1 SNP rs1015451 可作为 PVI 后 AF 复发的新型遗传标志物。
