No primary association between the 308 polymorphism in the tumor necrosis factor alpha promoter region and insulin-dependent diabetes mellitus

Whereas TNF-alpha has been implicated in the pathogenesis of IDDM, its possible role as a primary genetic susceptibility factor has not been well investigated. In this study, we analyzed a biallelic polymorphism in the TNF-alpha promotor region in a large collection of IDDM patients and controls ascertained from two ethnic populations (U.S. Caucasians and Chinese in Taiwan). We report that the associations with TNF-alpha: are due to linkage disequilibrium between TNF-a and che DR3-DQB1*0201 haplotype in both ethnic populations. Our analyses of extended haplotypes for the HLA region further substantiate the conclusion that no primary association exists between IDDM and the TNF-alpha promoter polymorphism.