A Genetic Risk Score for Atrial Fibrillation Predicts the Response to Catheter Ablation
A Genetic Risk Score for Atrial Fibrillation Predicts the Response to Catheter Ablation
复制标题
DOI：
10.4070/kcj.2018.0161
复制
发表时间：
2019-04-01
影响因子：
2.9
通讯作者：
Lim, Hong Euy
中科院分区：
文献类型：
--
作者：
Choe, Won-Seok;Kang, Jun Hyuk;Lim, Hong Euy
背景和目标：心房颤动（AF）易感位点与消融术后AF复发的相关性已有报道，尽管结果存在争议。在这项前瞻性队列分析中，我们的目的是调查是否遗传风险评分（GRS）可以预测心律的结果，导管消融术后的AF。方法：我们确定了20个AF易感单核苷酸多态性（SNP）和AF复发之间的关联导管消融术后746例（74%男性，年龄，59 +/- 11岁，56%阵发性AF）。通过对所选SNP的风险等位基因的未加权数目求和来计算GRS。A考克斯比例风险模型被用来确定GRS和房颤复发的风险之间的关联导管ablation.Results：房颤复发导管消融术后发生在168（22.5%）的主题，平均随访23个月。使用5个SNP（位于染色体4 q25 [PITX 2]的rs 1448818、rs 2200733、rs6843082、rs6838973和位于染色体16 q22 [ZFHX 3]的rs 2106261）计算GRS，这些SNP显示与AF复发存在中度相关性。GRS与AF复发显著相关（每个评分的风险比[HR]为1.13; 95%置信区间[CI]为1.03-1.24）。中度（GRS 4-6）和高风险患者（GRS 7-10）显示HR为2.00（95% CI，0.99-4.04）和2.66（95%CI，1.32-5.37）与低风险患者（GRS 0-3）相比。在韩国人群中，我们使用5个AF易感SNP的新型GRS与导管消融术后的AF复发密切相关，超出了临床风险因素。进一步的努力是必要的，以构建一个通用的，强大的遗传预测模型，可以指导最佳的治疗策略。
Background and Objectives: The association of susceptibility loci for atrial fibrillation (AF) with AF recurrence after ablation has been reported, although with controversial results. In this prospective cohort analysis, we aimed to investigate whether a genetic risk score (GRS) can predict the rhythm outcomes after catheter ablation of AF.Methods: We determined the association between 20 AF-susceptible single nucleotide polymorphisms (SNPs) and AF recurrence after catheter ablation in 746 patients (74% males; age, 59 +/- 11 years; 56% paroxysmal AF). A GRS was calculated by summing the unweighted numbers of risk alleles of selected SNPs. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation.Results: AF recurrences after catheter ablation occurred in 168 (22.5%) subjects with a median follow-up of 23 months. The GRS was calculated using 5 SNPs (rs1448818, rs2200733, rs6843082, rs6838973 at chromosome 4q25 [PITX2] and rs2106261 at chromosome 16q22 [ZFHX3]), which showed modest associations with AF recurrence. The GRS was significantly associated with AF recurrence (hazard ratio [HR] per each score, 1.13; 95% confidence interval [CI], 1.03-1.24). Patients with intermediate (GRS 4-6) and high risks (GRS 7-10) showed HRs of 2.00 (95% CI, 0.99-4.04) and 2.66 (95% CI, 1.32-5.37), respectively, compared to patients with low risk (GRS 0-3).Conclusions: Our novel GRS using 5 AF-susceptible SNPs was strongly associated with AF recurrence after catheter ablation in Korean population, beyond clinical risk factors. Further efforts are warranted to construct a generalizable, robust genetic prediction model which can guide the optimal treatment strategies.