Lack of Association of DMB Polymorphism with Insulin-Dependent Diabetes

• Published in: Journal of autoimmunity Vol. 10; no. 4; pp. 395 - 400
• Main Authors: Esposito, Laura, Lampasona, Vito, Bonifacio, Ezio, Bosi, Emanuele, Ferrari, Maurizio
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.08.1997; Elsevier
• Subjects: Alleles; Base Sequence; Biological and medical sciences; Case-Control Studies; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; DMB; DNA Primers - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Frequency; Genes, MHC Class II; Genetic Linkage; Haplotypes; Histocompatibility Antigens Class II; HLA class II; HLA-D Antigens - genetics; Humans; insulin-dependent diabetes mellitus; linkage disequilibrium; Male; Medical sciences; Middle Aged; Pedigree; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Risk Factors; TAP peptide transporter gene; DMB; TAP peptide transporter gene; HLA class II; insulin-dependent diabetes mellitus; linkage disequilibrium; Endocrinopathy; Human; Immunopathology; Antigen presentation; HLA-System; Genetic inheritance; Linkage; Pathogenesis; Class II histocompatibility antigen; Beta-Peptide chain; Autoimmune disease; HLA-DQ-Locus; Gene; Insulin dependent diabetes; Genetics; Molecular biology; Polymorphism
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1997.0144

Considerable evidence exists that the genes coding for the HLA class II DQ molecules in the MHC region are major contributors to genetic susceptibility in insulin-dependent diabetes. Located centromeric to the DQ loci are the genes encoding DMA and DMB, two class II-like molecules which play an essential role in the pathway leading to antigen presentation by HLA class II. In this study we have examined the distribution of the DMB allele and studied HLA DQA1-DQB1-TAP2-DMB haplotypes in 52 IDDM families and 65 un-related controls. DMB allele frequencies in IDDM and control subjects were not significantly different. DMB*0101 was present in 85% of patients vs. 76% of controls, DMB*0102 in 12 vs. 17%, DMB*0103 in 3 vs. 5%, DMB*0104 in 0 vs. 2%. The IDDM-susceptible MHC DQA1-DQB1 haplotypes found by analysis of IDDM families were not associated with specific DMB alleles. We conclude that the described DMB polymorphisms are not associated with IDDM susceptibility and DMB genotyping is unlikely to improve the assessment of genetic risk for IDDM.