Role of cytokine gene (IFN-γ, TNF-α, TGF-β1, IL-6, and IL-10) polymorphisms in pathogenesis of acute rheumatic fever in Turkish children

Eur J Pediatr. 2012 Jul;171(7):1103-8. doi: 10.1007/s00431-012-1689-5. Epub 2012 Feb 17.

Abstract

Acute rheumatic fever (ARF) is a delayed immunologically mediated sequela of throat infection by group A β-hemolytic streptococci. Inflammatory cytokines may play a pathogenic role in ARF. The objective of this study was to investigate the potential associations between interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and IL-10 gene polymorphisms and childhood ARF. Thirty-eight ARF patients and 40 age- and sex-matched healthy controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874), IL-6 (-174), TNF-α (-308), TGF-β1 (+10, +25), and IL-10 (-1082, -819, -592)]. Cytokine genotyping was performed by polymerase chain reaction sequence-specific primer methods. Patients with ARF had significantly higher frequencies of IFN-γ (+874) polymorphism in both TT genotype (p=0.0002) and T allele (p=0.0004). No statistically significant differences were observed in genotypes, haplotypes, and allele frequencies of IL-6, TNF-α, TGF-β1, and IL-10 genes between ARF and control groups (p>0.05). GG genotype frequency of TNF-α gene (low expression) was higher in patients who had previous ARF history (p=0.006). High expression of TGF-β1 (TT/GG, TC/GG) was more frequent in patients with CRP positivity (p=0.034). IL-6 CC genotype (low expression) frequency was higher in patients with tricuspid valve insufficiency (p=0.002), while IFN-γ TT genotype (high expression) frequency was higher in patients with mitral valve prolapse (p=0.049).

Conclusion: High expression of the IFN-γ gene may carry a higher risk for ARF in Turkish children, while IL-6, TNF-α, and TGF-β1 may have an impact in mediating some clinical and laboratory manifestations of the disease.

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genetic Markers
  • Genotype
  • Genotyping Techniques
  • Humans
  • Interferon-gamma / genetics*
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Rheumatic Fever / genetics*
  • Rheumatic Fever / immunology
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Turkey

Substances

  • Biomarkers
  • Genetic Markers
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma