POLYMORPHISMS OF TAP1 AND TAP2 GENES IN GERMAN PATIENTS WITH TYPE-1 DIABETES-MELLITUS

Type 1 diabetes mellitus (IDDM) is an autoimmune disorder in which the alleles HLA DQA10501-DQB1*0201 and DQA1*0301-DQB1*0302 confer strong susceptibility. The genes for transporters associated with antigen pr ocessing (TAP1 and TAP2) are located near HLA DQ and display only a li mited degree of polymorphism. Since polymorphisms of TAP might influen ce susceptibility to IDDM possibly by selection of different antigen p eptides, we investigated sequence variants of TAP1 and TAP2 genes in 1 20 German patients with IDDM and 218 random healthy German controls by polymerase chain reaction (PCR) followed by sequence-specific oligonu cleotide analysis (SSO), single-strand conformation polymorphism (SSCP ) analysis and amplification refractory mutation system (ARMS). TAP10 2011 (16% vs. 4% in controls, P = 0.001, RR = 5.0) and TAP20101 (96% vs. 69% in controls, P < 0.0001, RR = 10.6) showed a positive associat ion with IDDM. However, these associations disappeared when patients a nd controls were matched for predisposing HLA DQA1 or DQB1 alleles as well as for DRB10401. In conclusion, our findings indicate that the o bserved association of TAP variants with IDDM in German patients is du e to linkage disequilibrium with HLA DQ alleles/DRB104 subtypes.