A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha.
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.
University Department of Medicine, Royal Hallamshire Hospital, University of Sheffield, GB.
A G
AG
Wilson
C
C
Gordon
F S
FS
di Giovine
N
N
de Vries
L B
LB
van de Putte
P
P
Emery
G W
GW
Duff
D001323:Autoantibodies / Q000235:genetics; D001483:Base Sequence; D005260:Female; D015795:HLA-B8 Antigen / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D001323:Autoantibodies; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha