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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-3-4
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pubmed:abstractText |
IgA deficiency (IgAD) and common variable immunodeficiency (CVID) often co-occur in families, associating with chronic inflammatory diseases such as celiac disease (CD). ICOS (inducible co-stimulator) and CTLA4 (cytotoxic T-lymphocyte-associated protein-4) may be important in both disorders, as ICOS is necessary for Ig class-switching and CTLA4 negatively regulates T-cell activation. Linkage and association of CD with CTLA4-ICOS is well documented, we thus aimed to further pinpoint CD susceptibility by haplotype-tagging analysis. We genotyped 663 CD families from Finland and Hungary, 575 additional CD patients from Finland, Hungary and Italy; 275 Swedish and Finnish IgAD individuals and 87 CVID individuals for 14-18 genetic markers in CTLA4-ICOS. Association was found between CTLA4-ICOS and both IgAD (P=0.0015) and CVID (P=0.0064). We confirmed linkage of CTLA4-ICOS with CD (LOD 2.38, P=0.0005) and found association of CTLA4-ICOS with CD (P=0.0009). Meta-analysis of the IgAD, CVID and CD materials revealed intergenic association (P=0.0005). Disease-associated markers were associated with lower ICOS and higher CTLA4 expression, indicating that the risk haplotypes contain functional variants. In summary, we identified a novel shared risk locus for IgAD, CVID and CD, the first report of association between CTLA4-ICOS and IgAD. Association between CD and CTLA4-ICOS was also confirmed in a large European data set.
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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 |
Mar
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pubmed:issn |
1476-5470
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pubmed:author |
pubmed-author:AdányRR,
pubmed-author:DukesEE,
pubmed-author:EinarsdottirEE,
pubmed-author:HaimilaKK,
pubmed-author:HammarströmLL,
pubmed-author:KES JSJ,
pubmed-author:KaartinenTT,
pubmed-author:KaukinenKK,
pubmed-author:Korponay-SzaboI RIR,
pubmed-author:KoskinenL L ELL,
pubmed-author:KoskinenSS,
pubmed-author:KurppaKK,
pubmed-author:Pan-HammarströmQQ,
pubmed-author:PartanenJJ,
pubmed-author:PocsaiZZ,
pubmed-author:SaavalainenPP,
pubmed-author:ShawN ENE,
pubmed-author:SzélesGG,
pubmed-author:VattaSS,
pubmed-author:VenturaAA,
pubmed-author:ZibernaFF,
pubmed-author:de KauweAA
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pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
151-61
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19020530-Antigens, CD,
pubmed-meshheading:19020530-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:19020530-CTLA-4 Antigen,
pubmed-meshheading:19020530-Celiac Disease,
pubmed-meshheading:19020530-Common Variable Immunodeficiency,
pubmed-meshheading:19020530-Female,
pubmed-meshheading:19020530-Finland,
pubmed-meshheading:19020530-Genetic Linkage,
pubmed-meshheading:19020530-Genotype,
pubmed-meshheading:19020530-Humans,
pubmed-meshheading:19020530-Hungary,
pubmed-meshheading:19020530-IgA Deficiency,
pubmed-meshheading:19020530-Inducible T-Cell Co-Stimulator Protein,
pubmed-meshheading:19020530-Male,
pubmed-meshheading:19020530-Quantitative Trait Loci
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pubmed:year |
2009
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pubmed:articleTitle |
The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency.
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pubmed:affiliation |
Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland. katri.haimila@bts.redcross.fi
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Multicenter Study
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