TNF-308A and HLA-DR3 alleles contribute independently to susceptibility tosystemic lupus erythematosus

Objective. To evaluate the respective contributions of tumor necrosis facto r (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to syst emic lupus erythematosus (SLE). Methods, TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to asses s the magnitude of the susceptibility factors. The presence or absence of t he SLE classification criteria was determined and correlated with the TNF p romoter and HLA-DRB1 genotypes, Results. The frequency of the TNF-308A/A and 308G/A genotypes was significa ntly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 23 8A/A genotypes were equally prevalent in SLE patients and controls. The HLA -DR3 specificity (DRB1*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4), Stratification to correct for interdepend ence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 w ith SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlat ion was found between TNF promoter and HLA-DRB1 genotypes and any SLE class ification criterion or disease manifestation. Conclusion. TNF-308A and HLA-DR3 alleles are independent susceptibility fac tors for SLE.