The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes

HLA-DPB1 genotypes were determined for samples from 269 multiplex Caucasian families from the Human Biological Data Interchange. DRB1 and DQB1 loci we re also characterized, allowing assignment of DPB1 alleles to haplotypes an d calculation of linkage disequilibrium values. Frequencies for several DPB 1 alleles differed significantly between patients and affected family-based control subjects. Some differences were attributable to linkage disequilib rium with DR and DQ alleles, whereas others were not. DPB1*0301 and DPB1*02 02 alleles are predisposing for type 1 diabetes in these data, not only in analyses of individual alleles, but also in genotype analyses. DPB1*0402 ap pears protective; however, stratification analysis indicates that its prote ctive effect is specific for DR3 haplotypes. A protective role for DPB1*040 1 is suggested by genotype analysis. For increased statistical power, DPB1 alleles were pooled into three categories: susceptible, neutral, and protec tive after removal of effects due to linkage disequilibrium with DR-DQ. Ana lysis of these pools suggests that DPB1 primarily affects susceptibility to , rather than protection from, type 1 diabetes in a dominant fashion. This effect is more apparent in patients with genotypes other than the highest r isk DR3/DR4-DQB1*0302 genotype. These data support a role for the DPB1 locu s in conferring susceptibility to type 1 diabetes.