These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Several loci in the HLA class III region are associated with T1D risk after adjusting for DRB1-DQB1.
    Author: Valdes AM, Thomson G, Type 1 Diabetes Genetics Consortium.
    Journal: Diabetes Obes Metab; 2009 Feb; 11 Suppl 1(Suppl 1):46-52. PubMed ID: 19143814.
    Abstract:
    AIM: Several studies have indicated that genes in the human leucocyte antigen (HLA) region additional to the HLA class II DRB1-DQB1 contribute to type 1 diabetes (T1D) susceptibility. The aim of this study was to assess if markers in the class III Major Histocompatibility Complex (MHC) region are associated with T1D after accounting for linkage disequilibrium (LD) with DRB1-DQB1. METHODS: We investigated 356 single nucleotide polymorphisms (SNPs) in the class III region covering 1.1 megabases in two subsets of data: 289 Human Biological Data Interchange (HBDI) Caucasian families and 597 additional Caucasian families collected by the Type 1 Diabetes Genetics Consortium (T1DGC). Analysis conditioning on DRB1-DQB1 was performed using the overall conditional genotype method. RESULTS: Thirteen SNPs replicated in both subsets of the data and showed evidence of an additional effect on disease risk. Although some of the SNPs are in tight LD with each other, at least six of the associations were not because of LD with other class III markers. The strongest association within class III markers was with rs2395106 that maps 5' to the NOTCH4 gene, which has also been implicated in susceptibility to rheumatoid arthritis. The second association was with rs707915 mapping to the MSH5 gene, in a block of six markers significantly associated with T1D after adjusting for LD with DR-DQ. In total, six-independent associations within class III were observed although results were not adjusted for LD with class I. CONCLUSIONS: Our data confirm that the class III region is involved in T1D susceptibility and suggest that more than one gene in the region is involved.
    [Abstract] [Full Text] [Related] [New Search]