TAP2 polymorphisms in Australian multiple sclerosis patients.

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.