Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes
| Autor: | Sunanda R. Babu, Liping Yu, Desmond A. Schatz, Tihamer Orban, David Cuthbertson, Adina Zeidler, Jerry P. Palmer, Maria J. Redondo, George S. Eisenbarth, Jeffrey P. Krischer, Carla J. Greenbaum |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male musculoskeletal diseases medicine.medical_specialty Chromosomes Human Pair 6/genetics Adolescent Genotype endocrine system diseases Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) Human leukocyte antigen Biology medicine.disease_cause Biochemistry Autoantibodies/biosynthesis Autoimmunity Islets of Langerhans Endocrinology immune system diseases HLA-DQ Antigens Internal medicine Diabetes mellitus HLA-DQ medicine Humans Life Tables Child skin and connective tissue diseases Alleles Autoantibodies Type 1 diabetes Biochemistry (medical) Haplotype Autoantibody nutritional and metabolic diseases medicine.disease Survival Analysis Diabetes Mellitus Type 1 Haplotypes Diabetes Mellitus Type 1/genetics/pathology Child Preschool Immunology Disease Progression Chromosomes Human Pair 6 Female Follow-Up Studies |
| Zdroj: | Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| Popis: | Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic association with type 1 diabetes (T1DM) risk. OBJECTIVE: The objective of the study was to analyze whether HLA DQ alleles influence the development of antiislet autoantibodies, the progression to T1DM among autoantibody-positive relatives, or both. DESIGN: The Diabetes Prevention Trial-1 screened more than 90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody (ICA) expression between 1994 and 2002. SETTING: The study was conducted in the general community. PARTICIPANTS: The Diabetes Prevention Trial-1 found 2817 ICA-positive relatives who were tested for biochemical autoantibodies (GAD65, ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for progression to diabetes for up to 8 yr (median, 3.6 yr). MAIN OUTCOME MEASURE: Progression to T1DM was measured. RESULTS: High-risk DQ haplotypes and genotypes were associated with a higher percentage of relatives expressing multiple biochemical autoantibodies and higher T1DM risk (e.g., respectively, 59 and 36% at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype). The number of autoantibodies expressed significantly increased T1DM risk and across different DQ genotypes, autoantibody positivity directly correlated with diabetes risk. However, multivariate analyses indicated that the influence of most genotypes on T1DM risk was not independent from autoantibody expression, with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic combinations conferred 5-yr diabetes risks significantly lower (e.g. 7%-DQA1*0201-DQB1*0201/DQA1*0501-DQB1*0201 and 14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201) than when those haplotypes were found in other combinations. CONCLUSION: HLA DQ alleles determine autoantibody expression, which is correlated with diabetes progression. Among autoantibody-positive relatives, most HLA DQ genotypes did not further influence T1DM risk. |
| Databáze: | OpenAIRE |
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