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Functional promoter −1816C>G variant of RANKL predicts risk and prognosis of lone atrial fibrillation

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Abstract

Receptor activator of nuclear factor-κB ligand (RANKL) had been confirmed contributing to the development and progression of AF by regulating atrial structural remodeling. But the involved genetic mechanism is unknown. We intended to explore the association between the polymorphism RANKL −1816C>G (rs7984870) and susceptibility and prognosis of lone AF. RANKL rs7984870 was genotyped in a case–control study of 828 patients and 834 controls in Chinese population. The CG and/or CC genotypes had an increased lone AF risk [adjusted odds ratio (OR) 1.20 for CG, OR 2.16 for CC, and OR 1.55 for CG/CC], compared with the GG genotype. Moreover, patients carrying CG/CC genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying GG genotype. In a genotype–phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial RANKL expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CG and GG genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the −1816 C/C allele than that of the −1816 G/G allele. These results suggested that RANKL rs7984870 is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of RANKL in AF.

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Acknowledgements

The authors thank Dr. Ruyang Zhang (Department of Biostatistics, Nanjing Medical University, Nanjing, China) for his statistical assistance.

Funding

This work was supported in part by Jiangsu Provincial Medical Youth Talent [QNRC2016034], Jiangsu Province Health Department Program Grant [Z201411], Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health [JQX14006 and YKK17066].

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Author notes

  1. Hailong Cao and Wei Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China

    Hailong Cao, Qing Zhou & Dongjin Wang

  2. Department of Cardiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

    Wei Xu, Xin Chen & Rongfang Lan

  3. Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yijiang Chen

Authors
  1. Hailong Cao
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  2. Wei Xu
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  3. Xin Chen
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  4. Qing Zhou
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  5. Rongfang Lan
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  6. Yijiang Chen
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  7. Dongjin Wang
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Correspondence to Dongjin Wang.

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Cao, H., Xu, W., Chen, X. et al. Functional promoter −1816C>G variant of RANKL predicts risk and prognosis of lone atrial fibrillation. Heart Vessels 34, 151–158 (2019). https://doi.org/10.1007/s00380-018-1222-5

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  • DOI: https://doi.org/10.1007/s00380-018-1222-5

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