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To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean population, we investigated the frequencies of the TNFB and HLADRB1 alleles in 281 controls and 97 SLE patients, including 56 patients with nephritis and 41 patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs 28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2% vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients. After stratification for each HLADRB1 allele, SLE with nephritis showed a higher frequency of TNFB*2 homozygote compared with the corresponding controls in DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote may be a strong susceptibility gene of SLE with nephritis in the Korean population.