POLYMORPHISMS IN THE TNF GENE-CLUSTER AND MHC SEROTYPES IN THE WEST OF SCOTLAND

We examined the distribution of polymorphic elements within the tumor necrosis factor (TNF) gene cluster in 105 unrelated individuals and de termined their relationship to class I and class II major histocompati bility complex (MHC) antigens, and to the highly polymorphic microsate llites TNFa and TNFb. The data demonstrate the contribution of element s within the TNF cluster to two extended haplotypes which are recogniz ed to straddle the MHC. The A1.B8.DR3 haplotype appears to contain the TNF alleles TNFa2, TNFb3, LT.Nco-1.B1, and TNF-308.2, while the A3.B 7.DR2 haplotype is associated with the TNF alleles TNFa11, TNFb6, TNFc 1, LT.Nco-1.B2, LT.AspH1.1, TNF-308.1, and TNFe1. The presence of oth er extended associations which covered smaller parts of the MHC was al so suggested. In most cases, the associations described here were in k eeping with previously described extended haplotypes which dominate th e structure of the MHC, but these did not always match completely. Tak en together, these data suggest that the structure of the TNF locus is well integrated into the rest of the MHC but that important ethnic di fferences may exist.