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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

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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.

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Conflict of interest

The authors do not have any financial relationship with the organization that sponsored the research.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, University of Gaziantep, Universite Bulvari, 27310, Gaziantep, Turkey

    Nilgun Col-Araz

  2. Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Sacide Pehlivan, Sibel Oguzkan-Balci & Tugce Sever

  3. Department of Pediatric Cardiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Osman Baspinar

  4. Department of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Ayse Balat

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  1. Nilgun Col-Araz
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  2. Sacide Pehlivan
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  4. Sibel Oguzkan-Balci
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  5. Tugce Sever
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  6. Ayse Balat
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Correspondence to Nilgun Col-Araz.

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Col-Araz, N., Pehlivan, S., Baspinar, O. et al. 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 171, 1103–1108 (2012). https://doi.org/10.1007/s00431-012-1689-5

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  • DOI: https://doi.org/10.1007/s00431-012-1689-5

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