TUMOR-NECROSIS-FACTOR ALPHA-308 GENE VARIANTS IN RELATION TO MAJOR HISTOCOMPATIBILITY COMPLEX ALLELES AND FELTYS-SYNDROME

The location of the human TNF genes within the MHC complex has prompted much speculation about the role of TNF alleles in the etiology of MHC-associated autoimmune diseases. On sequencing the 5' regulatory region of the human TNFA gene a G (TNFA(-308G)) to A (TNFA(-308A)) transition polymerphism at position -308 was discovered. We have developed a simple PCR assay to facilitate the screening of the -308 polymorphism ar the DNA level. In view of the possible linkage between the TNFA(-308A) allele and a certain MHC type, TNFA-308 genotypes in HLA-typed healthy individuals (n = 88) were determined. A statistically significant association between the TNFA(-308A) allele and HLA-DRS, DQB1(*)0201, DQA1(*)0501, A1, B8, and the NcoI 5.5-kb RFLP of the TNFB gene was observed. In addition, we determined the frequency of the TNFA(-308A) allele in patients with FS (n = 13), an HLA-DR4-associated disease. In this study, no association was found of Felty's syndrome with the TNFA(-308A) allele, indicating that this allele does not appear to be a susceptibility factor for FS.