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Association study of a functional variant of TNF-α gene and serum TNF-α level with the susceptibility of congenital heart disease in a Chinese population
  1. Jun Pan1,
  2. Jiang Hu2,
  3. Xusheng Qi1,
  4. Liqin Xu1
  1. 1 Pediatrics, Taihe Hospital, Shiyan, China
  2. 2 Oncology, Taihe Hospital, Shiyan, China
  1. Correspondence to Dr Jun Pan, Pediatrics, Taihe Hospital, Shiyan 442000, China; panjunhb{at}


Background Congenital heart disease (CHD) is among the leading causes of infant death worldwide. Although shortage of folate has been found potentially to contribute to CHD in the embryo, the aetiology of CHD was not completely understood. Inflammation and altered immune processes are involved in all forms of cardiac malformation, including CHD. Tumour necrosis factor-α (TNF-α), was involved in the pathogenesis of multiple kinds of heart diseases. However, no studies have systematically evaluated the associations of genetic variants of TNF-α with susceptibility of CHD.

Methods A case-control study was conducted to evaluate the associations between tagSNPs of TNF-α and CHD susceptibility. Serum level of TNF-α was assessed using ELISA. The dual luciferase reporter assay was used to evaluate the functional significance of variant rs1800629 on TNF-α transcriptional activity.

Results We found rs1800629 was significantly correlated with increased CHD susceptibility (OR: 1.72, 95% CI 1.26 to 2.36, p=0.001). Serum levels of TNF-α were significantly higher in CHD group (9.09±1.90 pg/mL) than that in control group (6.12±1.56 pg/mL, p<0.001). The AA genotype and AG genotype of rs1800629 was associated with higher serum TNF-α level, compared with GG genotype. The dual luciferase reporter assay showed that promoter activity was significantly increased by 57% and 76% for plasmids containing the minor A allele compared with the major G allele in H9c2 and HEK 293T, respectively.

Conclusion These results indicate that higher level of serum TNF-α increases risk of CHD, while TNF-α rs1800629 A allele might contribute to higher risk for CHD due to the increase in TNF-α expression.

  • congenital heart defects
  • rs1800629
  • polymorphism
  • TNF-α
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  • JP and JH contributed equally.

  • Contributors JP and JH conceived and designed the experiments. JH, XQ and LX performed the experiments. XQ analysed the data. JP and JH wrote the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Parent(s)/guardian(s) consent obtained.

  • Ethics approval The study protocol was approved by the Medical Ethics Committee of Hubei Shiyan Taihe Hospital (3854).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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