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日本人群中射频导管消融术后房颤复发的全基因组关联研究。

Genome-Wide Association Study of Atrial Fibrillation Recurrence After Radiofrequency Catheter Ablation in a Japanese Population.

作者信息

Sakai Takumi, Furutani Motoki, Nakashima Mika, Ishibashi Naoki, Maeda Junji, Oguri Naoto, Miyamoto Shogo, Miyauchi Shunsuke, Okamura Sho, Okubo Yousaku, Tokuyama Takehito, Oda Noboru, Mitsumori Risa, Niida Shumpei, Ozaki Kouichi, Shigemizu Daichi, Nakano Yukiko

机构信息

Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

出版信息

J Cardiovasc Electrophysiol. 2025 Jul;36(7):1494-1503. doi: 10.1111/jce.16674. Epub 2025 Apr 28.

Abstract

INTRODUCTION

Catheter ablation of atrial fibrillation (AF) is an established treatment; however, recurrence remains a major issue.

METHODS

This study included 606 patients with AF who underwent catheter ablation in Hiroshima University Hospital, including 143 and 463 patients with and without AF recurrence within 3 years after ablation, respectively. A logistic regression analysis and genome-wide association study (GWAS) were conducted to identify the clinical and genetic factors, respectively, associated with the AF recurrence risk.

RESULTS

A logistic regression analysis revealed persistent AF, nonpulmonary vein AF triggers, the N-terminal pro-brain natriuretic peptide level, and the left atrial volume before catheter ablation were significant factors for recurrence (false discovery rate < 0.05). Additionally, six variants (rs2106865, rs12577119, rs12574466, rs4902609, rs8027532, and rs2032303) were associated with the AF recurrence risk, based on the GWAS results' suggestive significance (p < 5 × 10). An expression quantitative trait locus analysis revealed a significant association between rs2106865 and ATP-binding cassette subfamily C member 8 (ABCC8) expression in heart tissues (atrial appendage and left ventricle). A linear regression analysis demonstrated a significant association between the ABCC8 variant rs2106865 and left atrium volume before ablation. Finally, the Cox proportional hazard model showed a significant association between the ABCC8 variant and AF recurrence (p = 1.30 × 10 by log-rank test; hazard ratio 1.74, 95% confidence interval 1.38-2.20).

CONCLUSIONS

Our findings, which highlight both the clinical and genetic factors associated with AF recurrence in Japanese patients, may contribute to future efforts to improve treatment strategies for AF.

摘要

引言

导管消融治疗心房颤动(AF)已成为一种既定的治疗方法;然而,复发仍然是一个主要问题。

方法

本研究纳入了606例在广岛大学医院接受导管消融的房颤患者,其中分别有143例和463例在消融后3年内出现和未出现房颤复发。分别进行逻辑回归分析和全基因组关联研究(GWAS)以确定与房颤复发风险相关的临床和遗传因素。

结果

逻辑回归分析显示,持续性房颤、非肺静脉房颤触发因素、N末端脑钠肽前体水平以及导管消融前的左心房容积是复发的重要因素(错误发现率<0.05)。此外,根据GWAS结果的提示性意义(p<5×10),六个变体(rs2106865、rs12577119、rs12574466、rs4902609、rs8027532和rs2032303)与房颤复发风险相关。表达定量性状基因座分析显示rs2106865与心脏组织(心耳和左心室)中的ATP结合盒亚家族C成员8(ABCC8)表达之间存在显著关联。线性回归分析表明ABCC8变体rs2106865与消融前左心房容积之间存在显著关联。最后,Cox比例风险模型显示ABCC8变体与房颤复发之间存在显著关联(对数秩检验p=1.30×10;风险比1.74,95%置信区间1.38-2.20)。

结论

我们的研究结果突出了日本患者房颤复发相关的临床和遗传因素,可能有助于未来改进房颤治疗策略的努力。

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