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Heart and Vessels

, Volume 34, Issue 1, pp 151–158 | Cite as

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

  • Hailong Cao
  • Wei Xu
  • Xin Chen
  • Qing Zhou
  • Rongfang Lan
  • Yijiang Chen
  • Dongjin WangEmail author
Original Article
  • 66 Downloads

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.

Keywords

Receptor activator of nuclear factor-κB ligand Lone atrial fibrillation Genetic variation Susceptibility Prognosis 

Notes

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].

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose.

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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Hailong Cao
    • 1
  • Wei Xu
    • 2
  • Xin Chen
    • 2
  • Qing Zhou
    • 1
  • Rongfang Lan
    • 2
  • Yijiang Chen
    • 3
  • Dongjin Wang
    • 1
    Email author
  1. 1.Department of Thoracic and Cardiovascular Surgerythe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  2. 2.Department of Cardiologythe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  3. 3.Department of Thoracic and Cardiovascular Surgerythe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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