INTERETHNIC DIFFERENCES IN THE ASSOCIATION OF TUMOR-NECROSIS-FACTOR PROMOTER POLYMORPHISMS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective, To assess the role of polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene in susceptibility to systemic lupus erythematosus (SLE). Methods, Two ethnically differe nt populations of patients with SLE (49 white from the UK and 49 black from South Africa) were genotyped for TNF-238 and TNF-308 polymorphis ms using amplification refractory mutation system-polymerase chain rea ction (PCR). HLA-DR genotypes were assigned to the patients and contro ls either serologically or by PCR and sequence specific oligonucleotid es. The frequencies of the respective variants were compared between p atients and ethnically matched controls. Results, No significant diffe rences were found in the frequency of the TNF-238 variants in either e thnic group. At TNF-308, the TNF2 variant was significantly increased (p = 0.04) in white patients with SLE compared to controls. However, T NF2 was strongly associated with HLA-DTZS (p = 0.00002), which also sh owed a strong trend of increase in the white patients (p = 0.06). In c ontrast, in the black patients with SLE in whom DR2 but not DR3 was in creased, the frequency of TNF2 was actually reduced rather than increa sed. Conclusion, The increase of TNF2 in Caucasians with SLE is most l ikely due to linkage disequilibrium between TNF2 and DR3. Furthermore, the observation that TNF2 seems to be reduced in blacks with SLE stro ngly suggests this polymorphism is not an independent risk factor for SLE. Overall, our data indicate that the TNF-238 and TNF-308 promoter polymorphisms do not confer susceptibility to SLE.