| Effects of non-HLA gene polymorphisms on development of islet autoimmunity and type 1 diabetes in a population with high-risk HLA-DR,DQ genotypes. | |
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MedLine Citation:
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PMID: 22315323 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children identified as having high-risk HLA-DR/DQ genotypes for type 1 diabetes. Of those, 109 developed IA and 61 progressed to diabetes. Study participants were genotyped for 20 non-HLA polymorphisms, previously confirmed as type 1 diabetes susceptibility loci. PTPN22 and UBASH3A predicted both IA and diabetes in regression models controlling for family history of type 1 diabetes and presence of HLA-DR3/4-DQB1*0302 genotype. In addition, PTPN2 predicted IA whereas INS predicted type 1 diabetes. The final multivariate regression models for both IA and type 1 diabetes included PTPN22, UBASH3A, and INS, in addition to family history of type 1 diabetes and HLA-DR3/4. In general population children, the most frequent combinations including these five significant predictors conferred hazard ratio of up to 13 for IA and >40 for type 1 diabetes. Non-HLA susceptibility alleles may help estimate risk for development of type 1 diabetes in the general population. These findings require replication in different populations. |
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Authors:
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Andrea K Steck; Randall Wong; Brandie Wagner; Kelly Johnson; Edwin Liu; Jihane Romanos; Cisca Wijmenga; Jill M Norris; George S Eisenbarth; Marian J Rewers |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-02-07 |
Journal Detail:
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Title: Diabetes Volume: 61 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-22 Completed Date: 2012-04-10 Revised Date: 2012-04-12 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 753-8 Citation Subset: AIM; IM |
Affiliation:
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Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA. andrea.steck@ucdenver.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics Autoimmunity* Diabetes Mellitus, Type 1 / genetics* Genotype HLA-DQ Antigens / genetics* HLA-DR Antigens / genetics* Humans Islets of Langerhans / immunology* Polymorphism, Single Nucleotide* Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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AI-050864/AI/NIAID NIH HHS; DK-050979/DK/NIDDK NIH HHS; DK-320083/DK/NIDDK NIH HHS; DK-57516/DK/NIDDK NIH HHS; N01-AI-15416/AI/NIAID NIH HHS; R01 DK032493-29/DK/NIDDK NIH HHS; R37-DK-32493/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/HLA-DQ Antigens; 0/HLA-DR Antigens; 0/UBASH3A protein, human; EC 3.1.3.48/PTPN22 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 22 |
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