title: Sequence analysis of the tumor necrosis factor gene in pediatric patients with autoimmunity.
abstract: Tumor necrosis factor-alpha (TNF) is a multifunctional protein hormone that contributes to host defense and perinatal immunologic development. Dysregulated TNF production, however, occurs during the pathogenesis of autoimmune diseases and may be inherent to their development. In animal models of autoimmunity, dysregulated TNF synthesis has resulted from mutations in TNF gene regulatory sequences, specifically those sequences involved in translational control of TNF gene expression. In this study, we have determined whether mutations in the TNF translational control sequences are present in pediatric patients with type I diabetes mellitus and connective tissue diseases. Blood samples were collected from 48 patients with connective tissue diseases, 32 patients with diabetes, and 29 controls. A 250-bp fragment of the translational control sequences present in the TNF 3'-untranslated region was amplified by the polymerase chain reaction, sequenced, and analyzed relative to the published TNF sequence. In this study, all patients and controls exhibited the normal sequence, with no insertions or deletions in the translational control motifs. We conclude that polymorphisms in the TNF 3'-untranslated region occur infrequently, if at all, in patients with diseases examined here.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
authors.forename: L
authors.initials: L
authors.lastname: Becker
authors.forename: T
authors.initials: T
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Fink
authors.forename: J
authors.initials: J
authors.lastname: Marks
authors.forename: G
authors.initials: G
authors.lastname: Lavandosky
authors.forename: B P
authors.initials: BP
authors.lastname: Giroir
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D003240:Connective Tissue Diseases / Q000235:genetics; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha