| Replication and further characterization of a Type 1 diabetes-associated locus at the telomeric end of the major histocompatibility complex. | |
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MedLine Citation:
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PMID: 21631897 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: We recently reported an association between Type 1 diabetes and the telomeric major histocompatibility complex (MHC) single nucleotide polymorphism (SNP) rs1233478. As further families have been analyzed in the Type 1 Diabetes Genetics Consortium (T1DGC), we tested replication of the association and, with more data, analyzed haplotypic associations. METHODS: An additional 2717 case and 1315 control chromosomes have been analyzed from the T1DGC, with human leukocyte antigen (HLA) typing and data for 2837 SNPs across the MHC region. RESULTS: We confirmed the association of rs1233478 (new data only: P=2.2E-5, OR=1.4). We also found two additional SNPs nearby that were significantly associated with Type 1 diabetes (new data only rs3131020: P=8.3E-9, OR=0.65; rs1592410: P=2.2E-8, OR=1.5). For studies of Type 1 diabetes in the MHC region, it is critical to account for linkage disequilibrium with the HLA genes. Logistic regression analysis of these new data indicated that the effects of rs3131020 and rs1592410 on Type 1 diabetes risk are independent of HLA alleles (rs3131020: P=2.3E-3, OR=0.73; rs1592410: P=2.1E-3, OR=1.4). Haplotypes of 12 SNPs (including the three highly significant SNPs) stratify diabetes risk (high risk, protective, and neutral), with high-risk haplotypes limited to approximately 20,000 bp in length. The 20,000-bp region is telomeric of the UBD gene and contains LOC729653, a hypothetical gene. CONCLUSIONS: We believe that polymorphisms of the telomeric MHC locus LOC729653 may confer risk for Type 1 diabetes. |
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Authors:
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Erin E Baschal; Suparna A Sarkar; Theresa A Boyle; Janet C Siebert; Jean M Jasinski; Katharine R Grabek; Taylor K Armstrong; Sunanda R Babu; Pamela R Fain; Andrea K Steck; Marian J Rewers; George S Eisenbarth |
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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 |
Journal Detail:
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Title: Journal of diabetes Volume: 3 ISSN: 1753-0407 ISO Abbreviation: J Diabetes Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-16 Completed Date: 2012-01-25 Revised Date: 2012-04-12 |
Medline Journal Info:
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Nlm Unique ID: 101504326 Medline TA: J Diabetes Country: Australia |
Other Details:
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Languages: eng Pagination: 238-47 Citation Subset: IM |
Copyright Information:
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© 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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Barbara Davis Center for Childhood Diabetes, University of Colorado-Denver, 1775 Aurora Ct., Aurora, CO 80045, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence DNA Replication Diabetes Mellitus, Type 1 / genetics* Female Gene Expression Profiling Gene Frequency Genetic Loci / genetics Genotype HLA Antigens / genetics Haplotypes* Humans Linkage Disequilibrium Logistic Models Major Histocompatibility Complex / genetics* Male Molecular Sequence Data Polymorphism, Single Nucleotide* Sequence Analysis, DNA Telomere / genetics Ubiquitins / genetics |
| Grant Support | |
ID/Acronym/Agency:
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AI050864/AI/NIAID NIH HHS; AI15416/AI/NIAID NIH HHS; K01 DK080193/DK/NIDDK NIH HHS; P30 DK57516/DK/NIDDK NIH HHS; R01 DK032493-29/DK/NIDDK NIH HHS; R01 DK32083/DK/NIDDK NIH HHS; R37 DK32493/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HLA Antigens; 0/UBD protein, human; 0/Ubiquitins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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