Dataset Information

Rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

ABSTRACT: OBJECTIVE:To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3A). RESULTS:UBASH3A allele A was associated with development of IA [hazard ratio (HR)?=?1.46, 95%CI?=?1.11-1.91, p?=?0.007] and diabetes (HR?=?1.84, 95%CI?=?1.28-2.64, p?=?0.001), controlling for presence of HLA-DR3/4,DQB1*0302 and having a first-degree relative (FDR) with T1D. The UBASH3A AA genotype conferred higher risk of persistent IA (12.7%) and diabetes (6.1%) by age 10 than for AG (7.7 and 3.1%, respectively) or GG (5.3 and 2.0%) genotype (p?=?0.009 for IA, p?=?0.0004 for diabetes). Among children with no family history of T1D, but HLA-DR3/4,DQB1*0302 and UBASH3A AA genotype, 35.9% developed IA and 50.6% developed diabetes by age 15. CONCLUSIONS:UBASH3A appears to be an independent predictor of IA and T1D in children, including those free of family history of T1D but carrying the HLA-DR3/4,DQB1*0302 genotype. If confirmed, UBASH3A may prove useful in T1D risk prediction and pre-screening of the general population children for clinical trials.

SUBMITTER: Johnson K

PROVIDER: S-EPMC4886718 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

Johnson Kelly K Wong Randall R Barriga Katherine J KJ Klingensmith Georgeanna G Ziegler Anette-G AG Rewers Marian J MJ Steck Andrea K AK

Pediatric diabetes 20120708 8

<h4>Objective</h4>To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D).<h4>Research design and methods</h4>The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3 ...[more]

PMID: 22776074

Similar Datasets

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

Rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

Publications

rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets