title: Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan.
abstract: OBJECTIVE
  Cytokine network alterations contribute strongly to the initiation and perpetuation of systemic lupus erythematosus (SLE). This study investigated the cytokines production and polymorphism association of cytokines with SLE in Taiwan. The cytokines investigated included tumor necrosis factor-alpha (TNF-alpha), TNF-beta (TNF-beta), interleukin (IL)-4, IL-10 and transforming growth factor-beta1 (TGF-beta1).
  
  
  METHODS
  Genotyping of different cytokine genes was performed using polymerase chain reaction and restriction fragment length polymorphism methods in 136 patients. The cytokine levels in the supernatants of cultures of peripheral blood mononuclear cells (PBMCs) were determined by enzyme immunoassay.
  
  
  RESULTS
  The rates of genotype polymorphism of TNF-beta +252, IL-4 -590 and IL-10 -819 were significantly correlated with SLE. However, only the genotype frequency of TNF-beta +252A was in accordance with Hardy-Weinberg equilibrium and significantly greater than in the normal group. The stimulated PBMC culture supernatants from TNF-beta +252A carriers produced lower levels of TNF-beta compared to TNF-beta +252G/G homozygotes. Moreover, TNF-beta levels in stimulated PBMC culture supernatants were negatively correlated with those of IL-4, IL-10 and TGF-beta1. It is possible that TNF-beta plays a modulatory role in the expression of these 3 cytokines.
  
  
  CONCLUSIONS
  TNF-beta +252A polymorphism, other than TNF-alpha, IL-4, IL-10, and TGF-beta1, is significantly associated with SLE in Taiwan.
authors.affiliation: Division of Allergy, Immunology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ling-Ying
authors.initials: LY
authors.lastname: Lu
authors.forename: He-Hsiung
authors.initials: HH
authors.lastname: Cheng
authors.forename: Ping-Kuang
authors.initials: PK
authors.lastname: Sung
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Jeng-Jung
authors.initials: JJ
authors.lastname: Yeh
authors.forename: Angela
authors.initials: A
authors.lastname: Chen
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D008233:Lymphotoxin-alpha; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4