TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production


SALLAKCI N., AKCURIN G., KOKSOY S., Kardelen F., UGUZ A., COSKUN M., ...Daha Fazla

JOURNAL OF AUTOIMMUNITY, cilt.25, sa.2, ss.150-154, 2005 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 2
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1016/j.jaut.2005.05.005
  • Dergi Adı: JOURNAL OF AUTOIMMUNITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.150-154
  • Anahtar Kelimeler: rheumatic fever, rheumatic heart disease, TNF-alpha, TGF-beta, polymorphism, HEART-DISEASE, MONONUCLEAR-CELLS, T-CELLS, ALLELES, CYTOKINES
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Previous studies suggested that abnormal regulation of TNF-alpha production may have a role in the pathogenesis of rheumatic fever (RF). Polymorphism at the promoter region of TNF-alpha gene (-308 A) has recently been shown to be associated with rheumatic heart disease (RHD) in Mexican patients. Although this polymorphism has long been shown to affect TNF-alpha gene expression in cell lines, its role in production of the cytokine in RF patients has not been studied. We therefore investigated TNFalpha G-308A single nucleotide polymorphism and its effect on TNF-alpha production in 71 Turkish RF patients and 89 ethnically matched healthy controls. The TNF-alpha-308A allele frequency was found to be significantly higher in RF patients (RHD + arthritis) than in healthy controls [p < 0.0032 Odds ratio (OR) = 3.4, 95% confidence interval (0) (1.5-7.7)]. When RHD patients were analyzed as a separate group, significant difference persisted [p < 0.0055, OR = 3.3, 95% CI (1.5-7.6)]. More importantly, ELISPOT analysis demonstrated that existence of A allele was associated with higher TNF-alpha production compared with G allele. Our data suggest that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop RF disease. (c) 2005 Elsevier Ltd. All rights reserved.