Dataset Information

Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes.

ABSTRACT: Autoreactive CD4+ T cells initiate the chronic autoimmune disease Type-1 diabetes (T1D), in which multiple environmental and genetic factors are involved. The association of HLA, especially the DR-DQ loci, with risk for T1D is well documented. However, the molecular mechanisms are poorly understood. In this review, we explore the structural characteristics of HLA-DQ and the role of HLA-DM function as they may contribute to an understanding of autoreactive T cell development in T1D.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC3756536 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes.

Zhou Zemin Z Jensen Peter E PE

Frontiers in immunology 20130829

Autoreactive CD4+ T cells initiate the chronic autoimmune disease Type-1 diabetes (T1D), in which multiple environmental and genetic factors are involved. The association of HLA, especially the DR-DQ loci, with risk for T1D is well documented. However, the molecular mechanisms are poorly understood. In this review, we explore the structural characteristics of HLA-DQ and the role of HLA-DM function as they may contribute to an understanding of autoreactive T cell development in T1D. ...[more]

PMID: 24009614

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Project description:ObjectiveThe Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and genotypes.Research design and methodsSix hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1 loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted to an affected child with the frequency of chromosomes not transmitted to any affected child.ResultsA number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes (ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402 (OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503 (OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02).ConclusionsSpecific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison of closely related DR-DQ haplotype pairs with different type 1 diabetes risks allowed identification of specific amino acid positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific HLA haplotypes can be influenced by the genotype context and that the trans-complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.

Dataset Information

Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes.

Publications

Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes.

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