Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes
| Autor: | Jinko Graham, Gisela Dahlquist, William Hagopian, G Blohmé, Jonathan B. Schaefer, Marta Janer-Villanueva, Leroy Hood, Lou Sheng Li, Åke Lernmark, CB Sanjeevi, Jerry P. Palmer, Ingrid Kockum, M Zarghami, Robert M. Lowe, Heather L. Day, Mona Landin-Olsson, Göran Sundkvist, Norman E. Breslow |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Adolescent Genotype Endocrinology Diabetes and Metabolism medicine.medical_treatment Human leukocyte antigen Biology Islets of Langerhans Risk Factors Seroepidemiologic Studies HLA-DQ Antigens Internal medicine Immunopathology Diabetes mellitus Internal Medicine medicine Humans Age of Onset Sex Distribution Child Autoantibodies geography Type 1 diabetes geography.geographical_feature_category Insulin Infant Newborn Autoantibody Infant Islet medicine.disease Diabetes Mellitus Type 1 Logistic Models Endocrinology Child Preschool Immunology Female Age of onset Biomarkers |
| Zdroj: | Diabetes. 51:1346-1355 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.51.5.1346 |
| Popis: | Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0–34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3′ end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development. |
| Databáze: | OpenAIRE |
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