Effects of the second HLA-DQ haplotype on the association with childhood insulin-dependent diabetes mellitus.

Analysis of HLA-DQ molecules in a large study comprising 425 consecutively diagnosed Swedish Caucasians with IDDM and 367 age, sex and geographically matched controls confirms previous observations that: (a) DQB10302-DQA10301 confer susceptibility in a dominant manner, except when they are associated with DQB10602-DQA10102; (b) DQB10501-DQA10201 does not confer susceptibility to IDDM in either homozygous or heterozygous combinations with any other DQ molecules except when it is in association with DQB10302-DQA10301; (c) heterozygous combinations of DQB10302-DQA10301 and DQB10501-DQA10201 confer the highest risk to IDDM; (d) in DQ2 positive patients being negative for DQ8 in second haplotype (n = 58) the susceptibility may be explained by DR, since all these patients were DR3 positive, or by unknown factors between DQ and DR and (e) DQB10602-DQA10102 confers protection in a dominant manner. This large study does not confirm the positive association previously observed in Norwegians between the DQ8/DQ4 genotype and IDDM, as this genotype was not significantly associated with IDDM in Swedish patients. The new findings in this study include (a) that DQ8/DQ6 (DQB10604-DQA10102) was associated with IDDM in Swedish patients and (b) analysis of individual amino acids in DQB1 chain does not fully explain susceptibility to IDDM.