title: Tumor necrosis factor microsatellite polymorphism influences the development of insulin dependency in adult-onset diabetes patients with the DRB1*1502-DQB1*0601 allele and anti-glutamic acid decarboxylase antibodies.
abstract: Recently, several studies have demonstrated that tumor necrosis factor microsatellite polymorphism (TNFalpha) contributes to the susceptibility of type 1 diabetes. This study investigates the influence of TNFalpha on the predisposition to insulin dependency in adult-onset diabetic patients with type 1 diabetes-protective human leukocyte antigen haplotypes. The TNFalpha of three groups of DRB1*1502DQB1*0601-positive diabetic patients who had initially been nonketotic and noninsulin dependent for more than 1 yr was analyzed. Group A included 11 antibodies to glutamic acid decarboxylase (GADab)-positive patients who developed insulin dependency within 4 yr of diabetes onset. Group B included 11 GADab-positive patients who remained noninsulin dependent for more than 12 yr. Group C included 12 GADab-negative type 2 diabetes, and a control group included 18 nondiabetic subjects. In the group C and control subjects, DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha13 allele. DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha12 allele among the group A patients, but not among the group B patients. Interestingly, sera from all patients with non-TNFalpha12 and non-TNFalpha13 in group B reacted with GAD65 protein by Western blot. These results suggest that TNFalpha is associated with a predisposition to progression to insulin dependency in GADab/DRB1*1502DQB1*0601-positive diabetic patients initially diagnosed with type 2 diabetes and that determination of these patients' TNFalpha genotype may allow for better prediction of their clinical course.
authors.affiliation: The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Obayashi
authors.forename: G
authors.initials: G
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Fukui
authors.forename: K
authors.initials: K
authors.lastname: Kamiuchi
authors.forename: A
authors.initials: A
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Ogata
authors.forename: T
authors.initials: T
authors.lastname: Kanaitsuka
authors.forename: H
authors.initials: H
authors.lastname: Shigeta
authors.forename: Y
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D016883:Diabetic Ketoacidosis / Q000235:genetics; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D004272:DNA, Mitochondrial; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha; D005968:Glutamate Decarboxylase