Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

PLoS One. 2016 Jul 5;11(7):e0158676. doi: 10.1371/journal.pone.0158676. eCollection 2016.


Background: Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.

Methods: Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.

Results: Two transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16-3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.

Conclusion: Transforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • NAV1.5 Voltage-Gated Sodium Channel / genetics
  • Polymorphism, Single Nucleotide*
  • Sick Sinus Syndrome / genetics*
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / genetics*


  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Transforming Growth Factor beta1

Grants and funding

This study was supported by funding (NSC 101-2314-B-039-042) from Taiwan National Science Council (Ministry of Science and Technology) ( JYC received the funding.