RESEARCH ARTICLE

Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population Rongfeng Zhang☯, Xiaochen Tian☯, Lianjun Gao☯, Huihua Li, Xiaomeng Yin, Yingxue Dong, Yanzong Yang*, Yunlong Xia* First Affiliated Hospital of Dalian Medical University, Dalian, China

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☯ These authors contributed equally to this work. * [email protected] (YY); [email protected] (YX)

Abstract OPEN ACCESS Citation: Zhang R, Tian X, Gao L, Li H, Yin X, Dong Y, et al. (2016) Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population. PLoS ONE 11(8): e0160467. doi:10.1371/ journal.pone.0160467 Editor: Zhi-Ying Wu, Huashan Hospital, Fudan University, CHINA

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.

Received: December 7, 2015 Accepted: July 20, 2016 Published: August 1, 2016 Copyright: © 2016 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This work was supported by International SæT Cooperation Program of China (2014DFA31930), website: http://www.istcp.org.cn; and National Natural Science Foundation of China (81270247), website: http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.

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

Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population.

PR interval variations have recently been associated with an increased risk of long-term atrial fibrillation (AF), heart block and all-cause mortality...
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