RGD Reference Report - The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. - Rat Genome Database

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The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency.

Authors: Haimila, K  Einarsdottir, E  De Kauwe, A  Koskinen, LL  Pan-Hammarstrom, Q  Kaartinen, T  Kurppa, K  Ziberna, F  Not, T  Vatta, S  Ventura, A  Korponay-Szabo, IR  Adany, R  Pocsai, Z  Szeles, G  Dukes, E  Kaukinen, K  Maki, M  Koskinen, S  Partanen, J  Hammarstrom, L  Saavalainen, P 
Citation: Haimila K, etal., Genes Immun. 2009 Mar;10(2):151-61. doi: 10.1038/gene.2008.89. Epub 2008 Nov 20.
RGD ID: 11344917
Pubmed: PMID:19020530   (View Abstract at PubMed)
DOI: DOI:10.1038/gene.2008.89   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CTLA4Humanceliac disease susceptibilityIAGP DNA:SNPs more ...RGD 
Ctla4Mouseceliac disease susceptibilityISOCTLA4 (Homo sapiens)DNA:SNPs more ...RGD 
Ctla4Ratceliac disease susceptibilityISOCTLA4 (Homo sapiens)DNA:SNPs more ...RGD 
ICOSHumanceliac disease susceptibilityIAGP DNA:SNP and haplotype: :rs10932037(human)RGD 
IcosRatceliac disease susceptibilityISOICOS (Homo sapiens)DNA:SNP and haplotype: :rs10932037(human)RGD 
IcosMouseceliac disease susceptibilityISOICOS (Homo sapiens)DNA:SNP and haplotype: :rs10932037(human)RGD 
CTLA4Humanimmunoglobulin alpha deficiency susceptibilityIAGP DNA:SNPs more ...RGD 
Ctla4Ratimmunoglobulin alpha deficiency susceptibilityISOCTLA4 (Homo sapiens)DNA:SNPs more ...RGD 
Ctla4Mouseimmunoglobulin alpha deficiency susceptibilityISOCTLA4 (Homo sapiens)DNA:SNPs more ...RGD 
ICOSHumanimmunoglobulin alpha deficiency susceptibilityIAGP DNA:SNPs more ...RGD 
IcosRatimmunoglobulin alpha deficiency susceptibilityISOICOS (Homo sapiens)DNA:SNPs more ...RGD 
IcosMouseimmunoglobulin alpha deficiency susceptibilityISOICOS (Homo sapiens)DNA:SNPs more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)
Icos  (inducible T-cell co-stimulator)

Genes (Mus musculus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)
Icos  (inducible T cell co-stimulator)

Genes (Homo sapiens)
CTLA4  (cytotoxic T-lymphocyte associated protein 4)
ICOS  (inducible T cell costimulator)


Additional Information