Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Chuden Hospital, Hiroshima, Japan.
PLoS One. 2019 Mar 6;14(3):e0213208. doi: 10.1371/journal.pone.0213208. eCollection 2019.
Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is known to cause a sarcoplasmic reticulum Ca2+ leak. We investigated the association between HRC Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients.
We enrolled PAF patients who underwent RFCA (N = 334 for screening and N = 245 for replication) and were genotyped for HRC SNP (rs3745297). The patient age was younger and rate of diabetes and hypertension lower in the PAF patients with Ser96Ala than in those without (TT/TG/GG, 179/120/35; 64±10/60±12/59±13 y, P = 0.001; 18.5/ 9.2/8.6%, P = 0.04 and 66.1/50.0/37.1%, P = 0.001, respectively). During a mean 19 month follow-up, 57 (17.1%) patients suffered from AF recurrences. The rate of an Ser96Ala was significantly higher in patients with AF recurrence than in those without in the screening set (allele frequency model: odds ratio [OR], 1.80; P = 0.006). We also confirmed this significant association in the replication set (OR 1.74; P = 0.03) and combination (P = 0.0008). A multivariate analysis revealed that the AF duration, sinus node dysfunction, and HRC Ser96Ala were independent predictors of an AF recurrence (hazard ratio [HR], 1.04, P = 0.037; HR 2.42, P = 0.018; and HR 2.66, P = 0.007, respectively).
HRC SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.
射频导管消融 (RFCA) 后心房颤动 (AF) 的复发仍然是一个严重的问题。钙处理对 AF 复发有相当大的影响。组氨酸丰富的钙结合蛋白 (HRC) 遗传单核苷酸多态性 (SNP)，rs3745297 (T>G，Ser96Ala)，已知会导致肌浆网 Ca2+ 泄漏。我们研究了 HRC Ser96Ala 与阵发性 AF (PAF) 患者 RFCA 后 AF 复发之间的关系。
我们招募了接受 RFCA 的 PAF 患者（筛查组 N = 334，复制组 N = 245），并对 HRC SNP（rs3745297）进行了基因分型。与没有 Ser96Ala 的患者相比，携带 Ser96Ala 的 PAF 患者年龄更小，糖尿病和高血压的发生率更低（TT/TG/GG，179/120/35；64±10/60±12/59±13 岁，P = 0.001；18.5/9.2/8.6%，P = 0.04 和 66.1/50.0/37.1%，P = 0.001）。在平均 19 个月的随访期间，57 名（17.1%）患者发生 AF 复发。在筛查组中，AF 复发患者的 Ser96Ala 发生率明显高于无复发患者（等位基因频率模型：优势比 [OR]，1.80；P = 0.006）。我们还在复制组（OR 1.74；P = 0.03）和组合组（P = 0.0008）中确认了这一显著关联。多变量分析显示，AF 持续时间、窦房结功能障碍和 HRC Ser96Ala 是 AF 复发的独立预测因素（风险比 [HR]，1.04，P = 0.037；HR 2.42，P = 0.018；和 HR 2.66，P = 0.007）。
HRC SNP Ser96Ala 是 RFCA 后 AF 复发的一个新的遗传标记。
