Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan.
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.
Lu
Ling-Ying
LY
Division of Allergy, Immunology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Cheng
He-Hsiung
HH
Sung
Ping-Kuang
PK
Tai
Ming-Hong
MH
Yeh
Jeng-Jung
JJ
Chen
Angela
A
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
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