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Region Hovedstaden - en del af Københavns Universitetshospital
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Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes

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  1. Specific IgE positivity against inhalant allergens and development of autoimmune disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Iodine and tri-iodo-thyronine reduce the incidence of type 1 diabetes mellitus in the autoimmune prone BB rats

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

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  4. Thyroid peroxidase and thyroglobulin auto-antibodies in patients with newly diagnosed overt hypothyroidism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Characterization of plasma lipidomics in adolescent subjects with increased risk for type 1 diabetes in the DiPiS cohort

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Cost of Treating Skin Problems in Patients with Diabetes who Use Insulin Pumps and/or Glucose Sensors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Lipidomics of human adipose tissue reveals diversity between body areas

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect β-cell function at type 1 diabetes (T1D) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual β-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1**0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of β-cell function and HLA-DQB1 genotypes in T1D.

OriginalsprogEngelsk
TidsskriftAutoimmunity
Vol/bind44
Udgave nummer2
Sider (fra-til)107-114
Antal sider8
ISSN0891-6934
DOI
StatusUdgivet - 1 mar. 2011

ID: 55872941