title: Markers for risk of type 1 diabetes in relatives of Alsacian patients with type 1 diabetes.
abstract: BACKGROUND
  The cytotoxic T lymphocyte-associated antigen 4 gene (CTLA-4) encode the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. The receptor protein is a specific T lymphocyte surface antigen that is detected on cells only after antigen presentation. Thus, CTLA-4 is directly involved in both immune and autoimmune responses and may be involved in the pathogenesis of multiple T cell-mediated autoimmune disorders. There is polymorphism at position 49 in exon 1 of the CTLA-4 gene, providing an A-G exchange. Moreover, we assessed the CTLA-4 49 (Thr/Ala) polymorphism in diabetic patients and first-degree relatives as compared to control subjects.
  
  
  METHODS
  Three loci (HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 first-degree relatives and 84 nondiabetic control subjects by means of PCR-RFLP.
  
  
  RESULTS
  A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) and DQA1 alleles encoding for Arg in position 52 was observed in diabetic subjects and first-degree relatives as compared to controls. The genotype and allele frequencies of these polymorphisms in type 1 diabetic patients and first-degree relatives differed significantly from those of controls (p < 0.001 and 0.05 respectively). CTLA-49 Ala alleles frequencies were 75.8% in type 1 diabetic patients and 68.1% in first-degree relatives in comparison to 35.7% in control subjects. The Ala/Ala genotype conferred a relative risk of 18.8 (p < 0.001).
  
  
  CONCLUSIONS
  The CTLA-4 49 Ala allele confers an increased risk of type 1 diabetes, independent of age and HLA-DQ genetic markers.
authors.affiliation: Centre Européen d'Etude du Diabète-Hĵpitaux Universitaires de Strasbourg. jean-claude.ongagna@wanadoo.fr
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Ongagna
authors.forename: Remi
authors.initials: R
authors.lastname: Sapin
authors.forename: Michel
authors.initials: M
authors.lastname: Pinget
authors.forename: Alain
authors.initials: A
authors.lastname: Belcourt
mesh_terms: D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000235:genetics; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D060908:CTLA-4 Antigen; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D005190:Family; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood* / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D018796:Immunoconjugates; D000069594:Abatacept