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http://purl.uniprot.org/citations/19073967http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19073967http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19073967http://www.w3.org/2000/01/rdf-schema#comment"

Background

Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared.

Methods

We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects.

Results

Three celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease.

Conclusions

A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.org/dc/terms/identifier"doi:10.1056/nejmoa0807917"xsd:string
http://purl.uniprot.org/citations/19073967http://purl.org/dc/terms/identifier"doi:10.1056/nejmoa0807917"xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Wijmenga C."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Wijmenga C."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Plagnol V."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Plagnol V."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"van Heel D.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"van Heel D.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Todd J.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Todd J.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Stevens H."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Stevens H."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Walker N.M."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Walker N.M."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Hunt K.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Hunt K.A."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"McManus R."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"McManus R."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Cooper J.D."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Cooper J.D."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Clayton D.G."xsd:string
http://purl.uniprot.org/citations/19073967http://purl.uniprot.org/core/author"Clayton D.G."xsd:string
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