Rau H, Nicolay A, Donner H, Usadel K H, Badenhoop K
Medical Department I, Division of Endocrinology, Diabetology and Metabolism, Centre of Internal Medicine, Klinikum of the Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Eur J Immunogenet. 1997 Jun;24(3):229-236. doi: 10.1111/j.1365-2370.1997.00266.x.
Type 1 diabetes mellitus (IDDM) is an autoimmune disorder in which the alleles HLA DQA10501-DQB10201 and DQA10301-DQB10302 confer strong susceptibility. The genes for transporters associated with antigen processing (TAP1 and TAP2) are located near HLA DQ and display only a limited degree of polymorphism. Since polymorphisms of TAP might influence susceptibility to IDDM possibly by selection of different antigen peptides, we investigated sequence variants of TAP1 and TAP2 genes in 120 German patients with IDDM and 218 random healthy German controls by polymerase chain reaction (PCR) followed by sequence-specific oligonucleotide analysis (SSO), single-strand conformation polymorphism (SSCP) analysis and amplification refractory mutation system (ARMS). TAP102011 (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 association with IDDM. However, these associations disappeared when patients and controls were matched for predisposing HLA DQA1 or DQB1 alleles as well as for DRB10401. In conclusion, our findings indicate that the observed association of TAP variants with IDDM in German patients is due to linkage disequilibrium with HLA DQ alleles/DRB104 subtypes.
1型糖尿病（IDDM）是一种自身免疫性疾病，其中等位基因HLA DQA10501-DQB10201和DQA10301-DQB10302具有很强的易感性。与抗原加工相关的转运蛋白基因（TAP1和TAP2）位于HLA DQ附近，仅表现出有限程度的多态性。由于TAP的多态性可能通过选择不同的抗原肽影响IDDM的易感性，我们通过聚合酶链反应（PCR），随后进行序列特异性寡核苷酸分析（SSO）、单链构象多态性（SSCP）分析和扩增阻滞突变系统（ARMS），研究了120例德国IDDM患者和218例随机选取的健康德国对照中TAP1和TAP2基因的序列变异。TAP102011（患者中占16%，对照中占4%，P = 0.001，相对风险率RR = 5.0）和TAP20101（患者中占96%，对照中占69%，P < 0.0001，RR = 10.6）与IDDM呈正相关。然而，当患者和对照根据易感的HLA DQA1或DQB1等位基因以及DRB10401进行匹配时，这些相关性消失。总之，我们的研究结果表明，在德国患者中观察到的TAP变异与IDDM的相关性是由于与HLA DQ等位基因/DRB104亚型的连锁不平衡所致。
