A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha

Abstract

We have investigated the significance of tumor necrosis factor alpha (TNF-alpha) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA-B, -DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti-Ro and anti-La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA-DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA-B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA-DR3 showed the strongest disease association, we could not demonstrate association of HLA-DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti-Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti-La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA-DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8-DR3 haplotype, TNF-alpha polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.

Association of transforming growth factor β1 and tumor necrosis factor α polymorphisms with anti‐SSB/La antibody secretion in patients with primary Sjögren's syndrome

“…Fifteen patients and 7 controls who were positive for DRB1*03 were negative for the TNF2 allele, and 13 patients and 4 controls who were positive for the TNF2 allele were negative for DRB1*03. The conflicting results concerning the independence of TNF2 and HLA-DR in the genetic predisposition to systemic lupus erythematosus (32,33) shows how difficult it is to evaluate the importance of linkage disequilibrium in the interaction of these 2 factors in susceptibility to human diseases.…”

Polimorfismo del TNF-alpha en autoinmunidad y tuberculosis.

“…El alelo TNF2 se ha asociado con susceptibilidad al LES en poblaciones caucásicas, tanto en desequilibrio de ligamiento con HLA-DR3 (45,46) como independientemente de este locus (47,48). Por el contrario, en población mexicana con alto porcentaje amerindio (49) o en africanos (46) no se ha observado tal asociación.…”

The genetics of systemic lupus erythematosus: putting the pieces together

“…Some evidence has been obtained for possible association with SLE and alleles at Bcl-2, CTLA4, the T cell receptors, prolactin, tumor necrosis factor (TNF) and TNF receptors. [92][93][94][95][96][97][98] Even in aggregate, however, these effects are too small to explain the genetics of SLE. Therefore, other genes still remain to be identified.…”