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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
38
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pubmed:dateCreated |
2006-9-20
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pubmed:abstractText |
Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. The genotype associated with the highest risk for T1D is the DR3/4-DQ8 (DQ8 is DQA1*0301, DQB1*0302) heterozygous genotype. We determined HLA-DR and -DQ genotypes at birth and analyzed DR3/4-DQ8 siblings of patients with T1D for identical-by-descent HLA haplotype sharing (the number of haplotypes inherited in common between siblings). The children were clinically followed with prospective measurement of anti-islet autoimmunity and for progression to T1D. Risk for islet autoimmunity dramatically increased in DR3/4-DQ8 siblings who shared both HLA haplotypes with their diabetic proband sibling (63% by age 7, and 85% by age 15) compared with siblings who did not share both HLA haplotypes with their diabetic proband sibling (20% by age 15, P < 0.01). 55% sharing both HLA haplotypes developed diabetes by age 12 versus 5% sharing zero or one haplotype (P = 0.03). Despite sharing both HLA haplotypes with their proband, siblings without the HLA DR3/4-DQ8 genotype had only a 25% risk for T1D by age 12. The risk for T1D in the DR3/4-DQ8 siblings sharing both HLA haplotypes with their proband is remarkable for a complex genetic disorder and provides evidence that T1D is inherited with HLA-DR/DQ alleles and additional MHC-linked genes both determining major risk. A subset of siblings at extremely high risk for T1D can now be identified at birth for trials to prevent islet autoimmunity.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-10371488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-10426387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-10438898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-10615959,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-1139259,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15240634,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15292346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15298352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15314696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15342014,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15677516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-15784469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-16186404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-2010218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-2895363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-3057885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-3816042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-6405504,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-6832798,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-8099884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-8224807,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-8817105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-8900244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16966600-9519723
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:AlyTheresa ATA,
pubmed-author:BabuSunanda RSR,
pubmed-author:BarkerJennifer MJM,
pubmed-author:BarrigaKatherine JKJ,
pubmed-author:EisenbarthGeorge SGS,
pubmed-author:ErlichHenry AHA,
pubmed-author:FainPamela RPR,
pubmed-author:FernandoMaria SMS,
pubmed-author:IdeAkaneA,
pubmed-author:JahromiMohamed MMM,
pubmed-author:MiaoDongmeiD,
pubmed-author:NorrisJill MJM,
pubmed-author:RewersMarian JMJ,
pubmed-author:YuLipingL
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14074-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16966600-Adolescent,
pubmed-meshheading:16966600-Child,
pubmed-meshheading:16966600-Child, Preschool,
pubmed-meshheading:16966600-Chromosomes, Human, Pair 6,
pubmed-meshheading:16966600-Diabetes Mellitus, Type 1,
pubmed-meshheading:16966600-Genetic Predisposition to Disease,
pubmed-meshheading:16966600-Genotype,
pubmed-meshheading:16966600-HLA-DR Antigens,
pubmed-meshheading:16966600-Haplotypes,
pubmed-meshheading:16966600-Humans,
pubmed-meshheading:16966600-Infant,
pubmed-meshheading:16966600-Islets of Langerhans,
pubmed-meshheading:16966600-Pedigree,
pubmed-meshheading:16966600-Phenotype,
pubmed-meshheading:16966600-Prospective Studies,
pubmed-meshheading:16966600-Risk Factors,
pubmed-meshheading:16966600-Survival Rate
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pubmed:year |
2006
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pubmed:articleTitle |
Extreme genetic risk for type 1A diabetes.
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pubmed:affiliation |
Barbara Davis Center for Childhood Diabetes and Human Medical Genetics Program, University Colorado Health Sciences Center, Aurora, CO 80045, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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