Associations of GAD65- and IA-2- autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings. The Belgian Diabetes Registry
| Autor: | Åke Lernmark, Frans Gorus, Frans Schuit, Patrick Goubert, Alberto Falorni, L Kaufman, Harry Dorchy, Daniel Pipeleers, C L Vandewalle, C. Semakula, Bart Van Der Auwera, Willy Coucke |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
musculoskeletal diseases
Adult Genetic Markers Male medicine.medical_specialty endocrine system diseases Adolescent Genotype Endocrinology Diabetes and Metabolism Human leukocyte antigen Gastroenterology Nuclear Family Belgium Glutamate Dehydrogenase immune system diseases Risk Factors Internal medicine Immunopathology Diabetes mellitus HLA-DQ Antigens Internal Medicine medicine Humans Insulin Registries Child Autoantibodies Advanced and Specialized Nursing business.industry Haplotype Autoantibody nutritional and metabolic diseases Infant medicine.disease Diabetes Mellitus Type 1 Child Preschool Immunology Female Radiobinding assay Restriction fragment length polymorphism business |
| Zdroj: | Diabetes care. 20(10) |
| ISSN: | 0149-5992 |
| Popis: | OBJECTIVE To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0–39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the 20- to 39-year age-group: 1) their prevalence was higher in carriers of DQA1*0301-DQB1*0302 (88 vs. 73% in non[DQA1*0301-DQB1*0302], P = 0.001), and 2) an association was found in patients lacking this haplotype but carrying DQA1*0501-DQB1*0201, together with INS I/I (87 vs. 54% vs. non[INS I/I], P = 0.003). Siblings of IDDM patients also presented the association of GAD65-Abs with DQA1*0301-DQB1*0302 (13 vs. 2% non[DQA1*0301-DQB1*0302], P < 0.001), while associations with the second genetic risk group could not yet be assessed. At the onset of IDDM, IA-2-Ab prevalence was higher in carriers of DQA1*0301-DQB1*0302 (69 vs. 39% non[DQA1*0301-DQB1*0302], P < 0.001) but not of DQA1*0501-DQB1*0201 or INS I/I. This association was present in both the 0- to 19- and the 20- to 39-year age-groups. It was also found in siblings of IDDM patients (4 vs. 0% non[DQA1*0301-DQB1*0302], P < 0.001). CONCLUSIONS Both GAD65- and IA-2-Abs exhibit higher prevalences in presence of HLA-DQ- and/or INS-genetic risk markers. Their respective associations differ with age at clinical onset, suggesting a possible usefulness in the identification of subgroups in this heterogeneous disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|