Association of TNFAIP3 polymorphism with rheumatic heart disease in Chinese Han population

Immunogenetics. 2009 Dec;61(11-12):739-44. doi: 10.1007/s00251-009-0405-8. Epub 2009 Nov 10.


In a pair-matched case-control study (239 versus 478) conducted in Chinese Han population, we investigated the association between tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene, tumor necrosis factor receptor-associated factor 1 (TRAF1) gene, complement component 5 (C5) gene, and rheumatic heart disease (RHD). We observed no association with RHD for the five tagging single nucleotide polymorphisms (tSNP) in the C5 gene, the three tSNPs in the TNFAIP3 gene, or the two tSNPs in the TRAF1 gene. However, we determined that the tSNP, rs582757, located at intron_5 of the TNFAIP3 gene, associated with RHD in Chinese Han population. Both the distribution of genotype and allele frequencies differed significantly between case and control subjects (p = 0.001 and p = 0.0004, respectively). The minor C allele reduced the risk of RHD with a per-allele odds ratio of 0.57 (0.42-0.78) for the additive model in univariate analysis (p = 0.000). Under a dominant model, CC/CT carriers had a 0.54-fold reduced risk of RHD (95% confidence interval 0.38-0.75, p = 0.000) than TT carriers. Therefore, we report a new genetic variant (rs582757) in the TNFAIP3 gene that associated with the prevalence of RHD in Chinese Han population. Further genetic and functional studies are required to identify the etiological variants in linkage disequilibrium with this polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Analysis of Variance
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • China / epidemiology
  • Complement C5 / genetics
  • DNA-Binding Proteins
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Rheumatic Heart Disease / ethnology
  • Rheumatic Heart Disease / genetics*
  • TNF Receptor-Associated Factor 1 / genetics
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Young Adult


  • Complement C5
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • TNF Receptor-Associated Factor 1
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3