Document Detail


Genetics of type 1 diabetes.
MedLine Citation:
PMID:  21205883     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic β cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed.
CONTENT: Although HLA class II alleles account for up to 30%-50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. These include the insulin, PTPN22, CTLA4, IL2RA, IFIH1, and other recently discovered loci. Genomewide association studies performed with high-density single-nucleotide-polymorphism genotyping platforms have provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remain to be performed. Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband.
SUMMARY: Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes.
Authors:
Andrea K Steck; Marian J Rewers
Related Documents :
6998613 - Application of the lod score method to detection of linkage between hla and juvenile in...
12410803 - Macrophages from high-risk hla-dqb1*0201/*0302 type 1 diabetes mellitus patients are hy...
6165313 - Iris neovascular tufts.
Publication Detail:
Type:  Journal Article     Date:  2011-01-04
Journal Detail:
Title:  Clinical chemistry     Volume:  57     ISSN:  1530-8561     ISO Abbreviation:  Clin. Chem.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  176-85     Citation Subset:  IM    
Affiliation:
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic rev...
Next Document:  Discerning nonrigid 3D shapes from motion cues.