Department of Electrophysiology, Heart Center, Leipzig, Germany.
J Am Coll Cardiol. 2010 Feb 23;55(8):747-53. doi: 10.1016/j.jacc.2009.11.041.
This study tested the hypothesis that chromosome 4q25 single-nucleotide polymorphisms (SNPs) associate with atrial fibrillation (AF) recurrence after catheter ablation.
Recent genome-wide association studies identified 2 SNPs on chromosome 4q25 associated with AF. Although the mechanisms underlying this increased risk are unknown, the closest gene, PITX2, is critical for myocardium development in the pulmonary veins.
A total of 195 consecutive patients (mean age 56 +/- 12 years, 73% male) with drug-refractory paroxysmal (78%) or persistent (22%) AF who underwent AF catheter ablation were included. Two SNPs, rs2200733 and rs10033464, were genotyped using real-time polymerase chain reaction and fluorescence resonance energy transfer. Serial 7-day Holter electrocardiographic recordings were acquired to detect AF recurrences.
Early recurrence of atrial fibrillation (ERAF) (within the first 7 days) was observed in 37%, whereas late recurrence of atrial fibrillation (LRAF) (between 3 and 6 months) occurred in 21% of the patients. None of the clinical or echocardiographic baseline characteristics were associated with ERAF or LRAF. In contrast, the presence of any variant allele increased the risk for both ERAF (odds ratio [OR]: 1.994, 95% confidence interval [CI]: 1.036 to 3.837, p = 0.039) and LRAF (OR: 4.182, 95% CI: 1.318 to 12.664, p = 0.011). In patients with ERAF, 45% had LRAF, as opposed to 8% in patients without ERAF (OR: 9.274, 95% CI: 3.793 to 22.678, p < 0.001).
Polymorphisms on chromosome 4q25 modulate the risk for AF recurrence after catheter ablation. This finding points to a potential role for stratification of AF ablation therapy or peri-interventional management by genotype.
本研究旨在验证染色体 4q25 单核苷酸多态性(SNP)与导管消融术后心房颤动(AF)复发相关的假设。
最近的全基因组关联研究发现,染色体 4q25 上的 2 个 SNP 与 AF 相关。尽管这种风险增加的机制尚不清楚,但最接近的基因 PITX2 对肺静脉心肌发育至关重要。
共纳入 195 例连续接受药物难治性阵发性(78%)或持续性(22%)AF 导管消融的患者(平均年龄 56±12 岁,73%为男性)。使用实时聚合酶链反应和荧光共振能量转移技术对 rs2200733 和 rs10033464 两个 SNP 进行基因分型。连续 7 天进行 Holter 心电图记录以检测 AF 复发。
37%的患者出现早期 AF 复发(EFRA)(术后 7 天内),21%的患者出现晚期 AF 复发(LRAF)(3 至 6 个月)。临床或超声心动图基线特征均与 EFRA 或 LRAF 无关。相反,任何变异等位基因的存在均增加 EFRA(优势比[OR]:1.994,95%置信区间[CI]:1.036 至 3.837,p=0.039)和 LRAF(OR:4.182,95%CI:1.318 至 12.664,p=0.011)的风险。在 EFRA 患者中,45%的患者出现 LRAF,而在无 EFRA 患者中仅为 8%(OR:9.274,95%CI:3.793 至 22.678,p<0.001)。
染色体 4q25 上的多态性调节导管消融术后 AF 复发的风险。这一发现表明,通过基因型对 AF 消融治疗或围手术期管理进行分层可能具有潜在作用。