HLA Class I and Genetic Susceptibility to Type 1 Diabetes
| Autor: | Josyf C. Mychaleckyj, Janelle A. Noble, Michael D. Varney, Anna Lisa Fear, Anthony Louey, Julie A. Lane, Joyce Carlson, Eva Lavant, Ana M. Valdes, Rebecca Rappner, Patrick Concannon, P. V. Moonsamy, Henry A. Erlich |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Linkage disequilibrium T-Lymphocytes Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism HLA-C Antigens Human leukocyte antigen Biology Linkage Disequilibrium 03 medical and health sciences 0302 clinical medicine Gene Frequency Insulin-Secreting Cells Genotype Genetics Internal Medicine HLA-B Antigens Humans Genetic Predisposition to Disease Allele Allele frequency Genotyping 030304 developmental biology 0303 health sciences Polymorphism Genetic HLA-A Antigens Histocompatibility Antigens Class I Haplotype Exons 3. Good health Diabetes Mellitus Type 1 Immunology Female |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db10-0699 |
| Popis: | OBJECTIVE We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes–associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10−11) and B*3906 (10.31; P = 4 × 10−10). Other significantly type 1 diabetes–associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes. |
| Databáze: | OpenAIRE |
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