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http://purl.uniprot.org/citations/17143607http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17143607http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Pathophysiological similarities between latent autoimmune diabetes in adults (LADA) and type 1 diabetes indicate an overlap in genetic susceptibility. HLA-DRB1 and HLA-DQB1 are major susceptibility genes for type 1 diabetes but studies of these genes in LADA have been limited. Our aim was to define patterns of HLA-encoded susceptibility/protection in a large, well characterised LADA cohort, and to establish association with disease and age at diagnosis.

Materials and methods

Patients with LADA (n = 387, including 211 patients from the UK Prospective Diabetes Study) and non-diabetic control subjects (n = 327) were of British/Irish European origin. The HLA-DRB1 and -DQB1 genes were genotyped by sequence-specific PCR.

Results

As in type 1 diabetes mellitus, DRB1 0301_DQB1 0201 (odds ratio [OR] = 3.08, 95% CI 2.32-4.12, p = 1.2 x 10(-16)) and DRB1 0401_DQB1 0302 (OR = 2.57, 95% CI 1.80-3.73, p = 4.5 x 10(-8)) were the main susceptibility haplotypes in LADA, and DRB1 1501_DQB1 0602 was protective (OR = 0.21, 95% CI 0.13-0.34, p = 4.2 x 10(-13)). Differential susceptibility was conferred by DR4 subtypes: DRB1 0401 was predisposing (OR = 1.79, 95% CI 1.35-2.38, p = 2.7 x 10(-5)) whereas DRB1 0403 was protective (OR = 0.37, 95% CI 0.13-0.97, p = 0.033). The highest-risk genotypes were DRB1 0301/DRB1 0401 and DQB1 0201/DQB1 0302 (OR = 5.14, 95% CI 2.68-10.69, p = 1.3 x 10(-8); and OR = 6.88, 95% CI 3.54-14.68, p = 1.2 x 10(-11), respectively). These genotypes and those containing DRB1 0401 and DQB1 0302 associated with a younger age at diagnosis in LADA, whereas genotypes containing DRB1 1501 and DQB1 0602 associated with an older age at diagnosis.

Conclusions/interpretation

Patterns of susceptibility at the HLA-DRB1 and HLA-DQB1 loci in LADA are similar to those reported for type 1 diabetes, supporting the hypothesis that autoimmune diabetes occurring in adults is an age-related extension of the pathophysiological process presenting as childhood-onset type 1 diabetes."xsd:string
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http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Clark A."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Walker M."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"McCarthy M.I."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Hattersley A.T."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Zeggini E."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Desai M."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Gillespie K.M."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Hitman G.A."xsd:string
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http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Holman R.R."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Levy J.C."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Bingley P.J."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/author"Horton V.A."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/pages"68-73"xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/title"An association analysis of the HLA gene region in latent autoimmune diabetes in adults."xsd:string
http://purl.uniprot.org/citations/17143607http://purl.uniprot.org/core/volume"50"xsd:string
http://purl.uniprot.org/citations/17143607http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17143607
http://purl.uniprot.org/citations/17143607http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17143607
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http://purl.uniprot.org/uniprot/#_A0A0A7C3I1-mappedCitation-17143607http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17143607
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