An association analysis of the HLA gene region in latent autoimmune diabetes in adults.
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1826268499742294016 |
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| author | Desai, M Zeggini, E Horton, V Owen, K Hattersley, A Levy, J Walker, M Gillespie, K Bingley, P Hitman, G Holman, R McCarthy, M Clark, A |
| author_facet | Desai, M Zeggini, E Horton, V Owen, K Hattersley, A Levy, J Walker, M Gillespie, K Bingley, P Hitman, G Holman, R McCarthy, M Clark, A |
| author_sort | Desai, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:10:37Z |
| format | Journal article |
| id | oxford-uuid:3e05a395-0d50-4747-aeb1-8b5c7ec615fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:10:37Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:3e05a395-0d50-4747-aeb1-8b5c7ec615fb2022-03-26T14:23:03ZAn association analysis of the HLA gene region in latent autoimmune diabetes in adults.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e05a395-0d50-4747-aeb1-8b5c7ec615fbEnglishSymplectic Elements at Oxford2007Desai, MZeggini, EHorton, VOwen, KHattersley, ALevy, JWalker, MGillespie, KBingley, PHitman, GHolman, RMcCarthy, MClark, A 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. |
| spellingShingle | Desai, M Zeggini, E Horton, V Owen, K Hattersley, A Levy, J Walker, M Gillespie, K Bingley, P Hitman, G Holman, R McCarthy, M Clark, A An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title | An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title_full | An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title_fullStr | An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title_full_unstemmed | An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title_short | An association analysis of the HLA gene region in latent autoimmune diabetes in adults. |
| title_sort | association analysis of the hla gene region in latent autoimmune diabetes in adults |
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