Bennetts B H, Teutsch S M, Heard R N, Dunckley H, Stewart G J
Department of Immunology, Westmead Hospital, Sydney, Australia.
J Neuroimmunol. 1995 Jun;59(1-2):113-21. doi: 10.1016/0165-5728(95)00033-x.
Polymorphism of the TAP2 gene locus, situated approximately 150 kb centromeric to the MHC class II loci HLA-DR, DQ was examined in 100 Australian patients with relapsing/remitting multiple sclerosis (MS), in 100 random controls and in 37 selected HLA-DRB11501-positive controls. The results were correlated with HLA class I and class II phenotypes. TAP2 encodes a protein involved in the transport and presentation of antigenic peptides by MHC class I molecules and hence is a candidate locus for a putative MS susceptibility gene either through functional interactions with class I alleles or as an explanation, via linkage disequilibrium (LD), for the known association between MS and the alleles DRB11501, DQA10102, DQB10602. Strong LD was found between the allele TAP201 and DRB11501 in both the MS and control populations. The MS-associated haplotype can therefore be extended to DRB11501, DQA10102, DQB10602, TAP201, and the putative gene locus could reside on the centromeric side of DQ. TAP2 typing, however, could not explain the DRB11501, DQA10102, DQB10602-negative patients in whom, interestingly, the frequency of TAP201 was decreased compared to controls. The results of this study exclude TAP2 as a locus for a necessary MS/MHC gene but indicate that an MS gene carried by the DRB11501, DQA10102, DQB1*0602 haplotype could reside centromeric of DQ.
对位于MHC II类基因座HLA - DR、DQ着丝粒侧约150 kb处的TAP2基因座多态性进行了检测，研究对象包括100例复发/缓解型多发性硬化症（MS）的澳大利亚患者、100例随机对照以及37例选定的HLA - DRB11501阳性对照。将结果与HLA I类和II类表型进行关联分析。TAP2编码一种参与MHC I类分子对抗原肽转运和呈递的蛋白质，因此，它可能是一个假定的MS易感基因位点，要么通过与I类等位基因的功能相互作用，要么通过连锁不平衡（LD）来解释MS与等位基因DRB11501、DQA10102、DQB10602之间已知的关联。在MS患者群体和对照群体中均发现等位基因TAP201与DRB11501之间存在强连锁不平衡。因此，与MS相关的单倍型可扩展为DRB11501、DQA10102、DQB10602、TAP201，并且假定基因位点可能位于DQ的着丝粒侧。然而，TAP2分型无法解释DRB11501、DQA10102、DQB10602阴性的患者情况，有趣的是，这些患者中TAP201的频率相较于对照有所降低。本研究结果排除了TAP2作为MS / MHC必要基因的位点，但表明由DRB11501、DQA10102、DQB1*0602单倍型携带的MS基因可能位于DQ的着丝粒侧。
