title: Major histocompatibility complex-encoded antigen processing gene polymorphism in IDDM.
abstract: 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.
authors.affiliation: Department of Microbiology, Stanford University School of Medicine, CA 94305-5402.
authors.forename: P M
authors.initials: PM
authors.lastname: van Endert
authors.forename: R S
authors.initials: RS
authors.lastname: Liblau
authors.forename: S D
authors.initials: SD
authors.lastname: Patel
authors.forename: L
authors.initials: L
authors.lastname: Fugger
authors.forename: T
authors.initials: T
authors.lastname: Lopez
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: H O
authors.initials: HO
authors.lastname: McDevitt
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D003062:Codon; D003546:Cysteine Endopeptidases; D017931:DNA Primers; D015342:DNA Probes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics; D012016:Reference Values; D015183:Restriction Mapping
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D003062:Codon; D017931:DNA Primers; D015342:DNA Probes; D000949:Histocompatibility Antigens Class II; D011506:Proteins; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases