HLA-DQβ Sequence Polymorphism and Genetic Susceptibility to IDDM
| Autor: | Brian Tait, Henry A. Erlich, Robert L Griffith, Gerald T. Nepom, Stephen Joel Scharf, Teodorica Bugawan |
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| Rok vydání: | 1990 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Molecular Sequence Data Biology chemistry.chemical_compound immune system diseases HLA-DQ Antigens Diabetes mellitus HLA-DQ HLA-DR4 Antigen Internal Medicine Genetic predisposition medicine HLA-DQ beta-Chains Humans Genetic Predisposition to Disease Amino Acid Sequence Allele Alleles Genetics Polymorphism Genetic Base Sequence Haplotype Nucleic acid sequence Chromosome Mapping DNA Control subjects medicine.disease Precipitin Tests Diabetes Mellitus Type 1 Haplotypes chemistry Electrophoresis Polyacrylamide Gel |
| Zdroj: | Diabetes. 39:96-103 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diacare.39.1.96 |
| Popis: | The analysis of HLA-DQ beta nucleotide sequence polymorphism in insulin-dependent diabetes mellitus (IDDM) patients and control subjects suggests a role for the DQ beta-chain in genetic susceptibility. Sequence determination and oligonucleotide hybridization was carried out on enzymatically amplified DNA from various HLA-DR-typed individuals, including the rare class of DR2+ patients. In the analysis of DQ beta variation in DR4, DRw6, and DR2 haplotypes, a correlation was observed between the presence of the negatively charged residue Asp at position 57 and low susceptibility and the presence of an Ala (DR4), Val (DRw6), or Ser (DR2) and higher susceptibility. However, important exceptions to this pattern have been identified in the analysis of heterozygous DR1/4 IDDM patients. In these individuals, susceptibility appears to correlate with specific DR beta l alleles (Dw4) on the DR4 haplotype, rather than with the DQ beta allele (DQB3.2) that contains Ala at position 57. The DQ beta alleles found in some Chinese IDDM patients also proved discordant with the position-57 correlations. Thus, although there is a general correlation between the residue at position 57 of the DQ beta-chain and IDDM susceptibility, these data do not support the notion that Asp 57 confers complete resistance or protection to IDDM. In general, these results suggest that IDDM susceptibility is conferred by specific combinations of DQ beta and DR beta sequences. |
| Databáze: | OpenAIRE |
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