COMPARATIVE-ANALYSIS OF THE GENETIC ASSOCIATIONS OF HLA-DRS AND TUMOR-NECROSIS-FACTOR-ALPHA WITH HUMAN IDDM

Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ al leles, but a pathogenic role for TNF-alpha in the class III region of the MHC has also been implied. We therefore tested whether there was a ny independent association between a biallelic TNF polymorphism and ID DM. The TNF2 allele was present in 61 of 114 (54%) IDDM patients compa red to 101 of 253 (40%) control subjects (odds ratio 1.73; p < 0.02). Stratification analysis in individuals matched for HLA-DR3 revealed, h owever, that this association was not independent of HLA-DR3 and is mo st likely to be a result of linkage disequilibrium between these allel es.