TBX5基因常见变异与中国汉族人群心房颤动的相关性
Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population.
作者信息
Zhang Rongfeng, Tian Xiaochen, Gao Lianjun, Li Huihua, Yin Xiaomeng, Dong Yingxue, Yang Yanzong, Xia Yunlong
机构信息
First Affiliated Hospital of Dalian Medical University, Dalian, China.
出版信息
PLoS One. 2016 Aug 1;11(8):e0160467. doi: 10.1371/journal.pone.0160467. eCollection 2016.
BACKGROUND
PR interval variations have recently been associated with an increased risk of long-term atrial fibrillation (AF), heart block and all-cause mortality. Genome-wide association studies have linked the PR interval with several common variants in the TBX5 gene. Several variants in the TBX5 gene, including rs7312625 and rs883079, have been associated with AF. The purpose of this study was to determine the association of single-nucleotide polymorphisms (SNPs) in the TBX5 gene, rs7312625 and rs883079, with AF in Chinese Han patients.
METHODOLOGY/PRINCIPAL FINDINGS: In this case-control association study, large cohorts of AF patients (n = 1132) and controls (n = 1206) were recruited from different hospitals. The genotyping was performed using a Rotor-Gene TM 6000 high-resolution melt system. Rs7312625, rs3825214 and rs883079 were analyzed. We found that SNP 3825214 was significantly associated with AF (P-obs = 0.002, odds ratio [OR] = 0.82), and lone AF (P-obs = 6.77x10-5, odds ratio [OR] = 0.71). SNP rs7312625 was significantly associated with lone AF (P-obs = 0.015, odds ratio [OR] = 1.27), although its association with AF was not significant. No significant association of SNP rs883079 with AF or lone AF was observed. Thus, we analyzed the interaction among these three loci. We demonstrated significant interaction among rs3825214, rs7312625 and rs883079. Four-locus risk alleles showed the highest odds ratio in combined rs3825214 and rs7312625 (P-obs<0.0001, odds ratio [OR] = 2.21). Six-locus risk alleles showed the highest odds ratio in combined rs3825214, rs7312625 and rs 883079(P-obs<0.0001, odds ratio [OR] = 2.35). Significance was established with the trend test (P<0.0001).
CONCLUSIONS
For the first time, we report the strong association of SNP rs3825214 in the TBX5 gene with AF and lone AF in a Chinese Han population. Rs7312625 was significantly associated with lone AF, and snp-snp interaction increased the risk of atrial fibrillation. Our data might provide new insights into understanding AF pathogenesis and designing novel genetic therapies for AF patients.
背景
近期研究表明，PR间期变化与长期心房颤动（AF）、心脏传导阻滞及全因死亡率风险增加有关。全基因组关联研究已将PR间期与TBX5基因中的多个常见变异联系起来。TBX5基因中的多个变异，包括rs7312625和rs883079，已被证实与AF相关。本研究旨在确定TBX5基因中的单核苷酸多态性（SNP）rs7312625和rs883079与中国汉族AF患者之间的关联。
方法/主要发现：在这项病例对照关联研究中，从不同医院招募了大量AF患者队列（n = 1132）和对照队列（n = 1206）。使用Rotor-Gene TM 6000高分辨率熔解系统进行基因分型。分析了rs7312625、rs3825214和rs883079。我们发现SNP 3825214与AF显著相关（P观察值 = 0.002，比值比[OR] = 0.82），与孤立性AF也显著相关（P观察值 = 6.77×10 -5，比值比[OR] = 0.71）。SNP rs7312625与孤立性AF显著相关（P观察值 = 0.015，比值比[OR] = 1.27），尽管其与AF的关联不显著。未观察到SNP rs883079与AF或孤立性AF有显著关联。因此，我们分析了这三个位点之间的相互作用。我们证明了rs3825214、rs7312625和rs883079之间存在显著的相互作用。四个位点的风险等位基因在rs3825214和rs7312625组合中显示出最高的比值比（P观察值<0.0001，比值比[OR] = 2.21）。六个位点的风险等位基因在rs3825214、rs7312625和rs 883079组合中显示出最高的比值比（P观察值<0.0001，比值比[OR] = 2.35）。通过趋势检验确定了显著性（P<0.0001）。
结论
我们首次报道了TBX5基因中的SNP rs3825214与中国汉族人群中的AF和孤立性AF有强关联。Rs7312625与孤立性AF显著相关，并且单核苷酸多态性-单核苷酸多态性相互作用增加了心房颤动的风险。我们的数据可能为理解AF发病机制和为AF患者设计新型基因治疗提供新的见解。
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