title: 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-DRB1*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.
authors.affiliation: Department of Immunology, Westmead Hospital, Sydney, Australia.
authors.forename: B H
authors.initials: BH
authors.lastname: Bennetts
authors.forename: S M
authors.initials: SM
authors.lastname: Teutsch
authors.forename: R N
authors.initials: RN
authors.lastname: Heard
authors.forename: H
authors.initials: H
authors.lastname: Dunckley
authors.forename: G J
authors.initials: GJ
authors.lastname: Stewart
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C071692:TAP2 protein, human