van Endert P M, Liblau R S, Patel S D, Fugger L, Lopez T, Pociot F, Nerup J, McDevitt H O
Department of Microbiology, Stanford University School of Medicine, CA 94305-5402.
Diabetes. 1994 Jan;43(1):110-7. doi: 10.2337/diab.43.1.110.
Susceptibility to insulin-dependent diabetes mellitus (IDDM) is greatly influenced by polymorphisms in the genes of the class II region of the human leukocyte antigen (HLA) complex. The complexity of this genetic association and the lack of a direct proof of involvement of HLA class II genes in human IDDM have continued to support speculation on a possible role of genes encoded in the close vicinity of these loci in IDDM. Because the recently discovered transporter associated with antigen processing (TAP) and large multifunctional protease (LMP) genes are encoded in the HLA class II region and are implicated in the processing of antigenic proteins for presentation by HLA class I molecules, they are additional candidates for a role in IDDM pathogenesis. We have analyzed genomic and coding sequence polymorphisms in the LMP2, TAP1, and TAP2 genes of 77 Danish IDDM patients and 102 control subjects. Although patients and control subjects did not differ in TAP1 and LMP2 alleles, we found a striking absence of the TAP2 allele B (long form) in IDDM patients. An analysis of the TAP2 alleles in individual DR types, however, revealed that this phenomenon is likely to be caused by linkage disequilibrium between the two loci. Thus, polymorphisms in the TAP and LMP genes are unlikely to be associated with IDDM.
胰岛素依赖型糖尿病（IDDM）的易感性受到人类白细胞抗原（HLA）复合体II类区域基因多态性的极大影响。这种遗传关联的复杂性以及缺乏HLA II类基因参与人类IDDM的直接证据，持续支持了关于这些基因座附近编码的基因在IDDM中可能作用的推测。由于最近发现的与抗原加工相关的转运体（TAP）和大型多功能蛋白酶（LMP）基因在HLA II类区域编码，并参与抗原蛋白的加工以供HLA I类分子呈递，它们是IDDM发病机制中发挥作用的额外候选基因。我们分析了77名丹麦IDDM患者和102名对照受试者的LMP2、TAP1和TAP2基因的基因组和编码序列多态性。尽管患者和对照受试者在TAP1和LMP2等位基因上没有差异，但我们发现IDDM患者中显著缺乏TAP2等位基因B（长形式）。然而，对个体DR类型中TAP2等位基因的分析表明，这种现象可能是由两个基因座之间的连锁不平衡引起的。因此，TAP和LMP基因的多态性不太可能与IDDM相关。
