title: 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.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Gaziantep, Universite Bulvari, 27310, Gaziantep, Turkey. naraz@gantep.edu.tr
authors.forename: Nilgun
authors.initials: N
authors.lastname: Col-Araz
authors.forename: Sacide
authors.initials: S
authors.lastname: Pehlivan
authors.forename: Osman
authors.initials: O
authors.lastname: Baspinar
authors.forename: Sibel
authors.initials: S
authors.lastname: Oguzkan-Balci
authors.forename: Tugce
authors.initials: T
authors.lastname: Sever
authors.forename: Ayse
authors.initials: A
authors.lastname: Balat
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012213:Rheumatic Fever / Q000235:genetics* / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D014421:Turkey
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma