| The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies. | |
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MedLine Citation:
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PMID: 20445565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The single nucleotide polymorphism 1858C>T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C>T allele in PTPN22 (PTPN22(CT+TT)) and T1D was modified by HLA. In addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison=0.007). The OR of association between PTPN22(CT+TT) and GADA-positive T1D declined with increasing HLA-risk category from 6.12 to 1.54 (P=0.003); no such change was detected in GADA-negative T1D (P=0.722) (P for comparison=0.001). However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT+TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA. We hypothesize that the altered T-cell function because of the PTPN22(1858C>T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis. |
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Authors:
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M Maziarz; M Janer; J C Roach; W Hagopian; J P Palmer; K Deutsch; C B Sanjeevi; I Kockum; N Breslow; A Lernmark; ; |
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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: 2010-05-06 |
Journal Detail:
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Title: Genes and immunity Volume: 11 ISSN: 1476-5470 ISO Abbreviation: Genes Immun. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-21 Completed Date: 2010-10-28 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 100953417 Medline TA: Genes Immun Country: England |
Other Details:
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Languages: eng Pagination: 406-15 Citation Subset: IM |
Affiliation:
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Department of Biostatistics, University of Washington, Seattle, WA 98195-7232, USA. marlenam@u.washington.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Age Factors Autoantibodies / immunology, metabolism* Case-Control Studies Child Child, Preschool Diabetes Mellitus, Type 1 / genetics* Female Genetic Predisposition to Disease / genetics* Genome-Wide Association Study Genotype Glutamate Decarboxylase / immunology* HLA Antigens / genetics* Humans Infant Infant, Newborn Male Odds Ratio Polymorphism, Single Nucleotide / genetics* Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics* Risk Assessment Sweden |
| Grant Support | |
ID/Acronym/Agency:
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5 P30 DK17047/DK/NIDDK NIH HHS; DK053004/DK/NIDDK NIH HHS; DK26910/DK/NIDDK NIH HHS; DK53004/DK/NIDDK NIH HHS; P01 DK053004-04/DK/NIDDK NIH HHS; R01 DK026190/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/HLA Antigens; EC 3.1.3.48/PTPN22 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 22; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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