TAP2 polymorphisms in Australian multiple sclerosis patients

Abstract

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-DRBl ∗1501-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 DRB1 ∗1501, DQA1 ∗0102, DQB1 ∗ 0602. Strong LD was found between the allele TAP2 ∗ 01 and DRB1 ∗ 1501 in both the MS and control populations. The MS-associated haplotype can therefore be extended to DRB1 ∗1501, DQA1 ∗0102, DQB1 ∗0602, TAP2 ∗01, and the putative gene locus could reside on the centromeric side of DQ. TAP2 typing, however, could not explain the DRB1 ∗ 1501, DQA1 ∗ 0102, DQB1 ∗ 0602-negative patients in whom, interestingly, the frequency of TAP2 ∗ 01 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 DRB1 ∗ 1501, DQA1 ∗ 0102, DQB1 ∗ 0602 haplotype could reside centromeric of DQ.