Major histocompatibility complex-encoded antigen processing gene polymorphism in IDDM

• Published in: Diabetes (New York, N.Y.) Vol. 43; no. 1; pp. 110 - 117
• Main Authors: VAN ENDERT, P. M, LIBLAU, R. S, PATEL, S. D, FUGGER, L, LOPEZ, T, POCIOT, F, NERUP, J, MCDEVITT, H. O
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 1994
• Subjects: Adult; Alleles; Amino Acid Sequence; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B, Member 3; ATP-Binding Cassette Transporters; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Codon; Cysteine Endopeptidases; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; DNA Primers; DNA Probes; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genes, MHC Class I; Genes, MHC Class II; Genetic aspects; Histocompatibility Antigens Class II - genetics; Humans; Major Histocompatibility Complex; Male; Medical sciences; Molecular Sequence Data; Physiological aspects; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Proteins - genetics; Reference Values; Restriction Mapping; Type 1 diabetes; Human; HLA-System; Restriction fragment length polymorphism; Major histocompatibility system; Class II histocompatibility antigen; Risk factor; Insulin dependent diabetes; Linkage equilibrium
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.43.1.110

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.