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http://purl.uniprot.org/citations/19143818http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19143818http://www.w3.org/2000/01/rdf-schema#comment"

Aim

Type 1 diabetes (T1D) is a complex trait for which variation in the classical human leucocyte antigen (HLA) loci within the Major Histocompatibility Complex (MHC) significantly influences disease risk. To date, HLA class II DR-DQ genes confer the strongest known genetic effect in T1D. HLA loci may also influence T1D through additional inherited or non-inherited effects. Evidence for the role of increased maternal-offspring HLA compatibility, and both parent-of-origin (POO) and non-inherited maternal HLA (NIMA) effects in autoimmune disease has been previously established. The current study tested hypotheses that classical HLA loci influence T1D through these mechanisms, in addition to genetic transmission of particular risk alleles.

Methods

The Type 1 Diabetes Genetics Consortium (T1DGC) cohort was of European descent and consisted of 2271 affected sib-pair families (total n = 11 023 individuals). Class I genes HLA-A, Cw and B, and class II genes HLA-DRB1, DQA1, DQB1, DPA1 and DPB1 were studied. The pedigree disequilibrium test was used to examine transmission of HLA alleles to individuals with T1D. Conditional logistic regression was used to model compatibility relationships between mother-offspring and father-offspring for all HLA loci. POO and NIMA effects were investigated by comparing frequencies of maternal and paternal transmitted and non-transmitted HLA alleles for each locus. Analyses were also stratified by gender of T1D-affected offspring.

Results

Strong associations were observed for all classical HLA loci except for DPA1, as expected. Compatibility differences between mother-offspring and father-offspring were not observed for any HLA loci. Furthermore, POO and NIMA HLA effects influencing T1D were not present.

Conclusions

Maternal-offspring HLA compatibility, POO and NIMA effects for eight classical HLA loci were investigated. Results suggest that these HLA-related effects are unlikely to play a major role in the development of T1D."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.org/dc/terms/identifier"doi:10.1111/j.1463-1326.2008.01006.x"xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/author"Thomson G."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/author"Barcellos L.F."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/author"Ramsay P.P."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/author"Bronson P.G."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/name"Diabetes Obes Metab 11 Suppl"xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/pages"74-83"xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/title"Analysis of maternal-offspring HLA compatibility, parent-of-origin and non-inherited maternal effects for the classical HLA loci in type 1 diabetes."xsd:string
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/volume"1"xsd:string
http://purl.uniprot.org/citations/19143818http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19143818
http://purl.uniprot.org/citations/19143818http://purl.uniprot.org/core/group"Diabetes Genetics Consortium"xsd:string
http://purl.uniprot.org/citations/19143818http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19143818
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