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Lookup NU author(s): Professor Mark Walker
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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 × 10-16) and DRB1*0401_DQB1*0302 (OR = 2.57, 95% CI 1.80-3.73, p = 4.5 × 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 × 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 × 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 × 10-8; and OR = 6.88, 95% CI 3.54-14.68, p = 1.2 × 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. © 2006 Springer-Verlag.
Author(s): Desai M, Zeggini E, Horton VA, Owen KR, Hattersley AT, Levy JC, Walker M, Gillespie KM, Bingley PJ, Hitman GA, Holman RR, McCarthy MI, Clark A
Publication type: Article
Publication status: Published
ISSN (print): 0012-186X
ISSN (electronic): 1432-0428
PubMed id: 17143607
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