title: Analysis of the coding and promoter regions of the autoantigen IA-2 in subjects with and without autoantibodies to IA-2.
abstract: Despite extensive studies on HLA polymorphism, there have been few, if any, studies on allelic forms or mutations in proteins that serve as autoantigens. The present experiments were designed to look for alterations in the coding and promoter regions of the autoantigen IA-2 in type one (insulin-dependent) diabetic patients with autoantibodies to IA-2 as compared with siblings without diabetes or autoantibodies to IA-2. Genomic DNA was used as a template and was amplified by polymerase chain reaction, with pairs of primers encompassing the promoter region and the 23 exons of the coding region of IA-2. A total of nine nucleotide changes were found in the coding region of the six type 1 diabetic patients; four were silent and five were missense changes, but all occurred in the extracellular domain of IA-2 to which autoantibodies are not directed. Few, if any, changes were found in the 5' upstream (-706 to +135) promoter region. The results of the experiments support the null hypothesis that differences among individuals in the nucleotide and amino acid sequences of the promoter and coding regions of IA-2, respectively, do not account for why some individuals develop autoantibodies to IA-2 and others do not.
authors.affiliation: Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4322, USA.
authors.forename: T
authors.initials: T
authors.lastname: Cai
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: J X
authors.initials: JX
authors.lastname: She
authors.forename: A L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000502:physiology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012016:Reference Values
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C096322:ICA512 autoantibody; D008565:Membrane Proteins; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8