Lack of association of the transporter associated with antigen processing with Japanese insulin-dependent diabetes mellitus.

The transporter associated with antigen processing (TAP) encoded in the major histocompatibility complex (MHC) class II region is a molecule required for endogenous antigen processing. We have typed TAP polymorphism in 95 Japanese patients with insulin-dependent diabetes mellitus (DDM) and 75 normal controls. Amino acid substitutions at positions 333 and 637 of TAP1 and at positions 379, 665, and 687 of TAP2 were typed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide method. In addition, DNA typing of human leukocyte antigen (HLA)-DQA1 and -DQB1 loci was performed by the PCR-restriction fragment length polymorphism method. There was no significant difference between IDDM patients and normal controls in the frequencies of TAP1 and TAP2 alleles. On the contrary, the HLA-DQ locus showed a strong association with IDDM in the same series of subjects. The frequencies of HLA-DQA10301 and -DQB10401 were increased significantly and those of HLA-DQA10103, -DQB10501, -DQB10601 and -DQB10602 were decreased significantly in Japanese IDDM patients compared with normal controls. Positive linkage disequilibrium was observed between HLA-DQB10303 and TAP2C and between HLA-DQB10401 and TAP2B. Negative linkage disequilibrium was observed between HLA-DQA10103 and TAP2A. Even when subjects with HLA-DQA10103, -DQA10301, -DQB10302, -DQB10303, and -DQB10401 were considered separately, no significant differences was found in the distribution of TAP1 and TAP2 alleles between IDDM patients and normal controls. We conclude that it is not TAP but HLA-DQ that exhibits a primary association with Japanese IDDM.