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 prompte d much speculation about the role of TNF alleles in the etiology of MH C-associated autoimmune diseases. On sequencing the 5' regulatory regi on of the human TNFA gene a G (TNFA(-308G)) to A (TNFA(-308A)) transit ion 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(-30 8A) allele and a certain MHC type, TNFA-308 genotypes in HLA-typed hea lthy 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 obs erved. In addition, we determined the frequency of the TNFA(-308A) all ele in patients with FS (n = 13), an HLA-DR4-associated disease. In th is study, no association was found of Felty's syndrome with the TNFA(- 308A) allele, indicating that this allele does not appear to be a susc eptibility factor for FS.