Modelling KIRHLA genotype disparities in type 1 diabetes

Authors

  • A. R. Van Der Slik,

    1. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
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  • B. Z. Alizadeh,

    1. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
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  • B. P. C. Koeleman,

    1. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    2. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
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  • B. O. Roep,

    Corresponding author
    1. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
      Bart O. Roep
      Department of Immunohaematology & Blood Transfusion
      Leiden University Medical Center, Leiden
      The Netherlands
      Tel: 31 715263869
      Fax: 31 71 5265267
      e-mail: boroep@lumc.nl
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  • M. J. Giphart

    1. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
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Bart O. Roep
Department of Immunohaematology & Blood Transfusion
Leiden University Medical Center, Leiden
The Netherlands
Tel: 31 715263869
Fax: 31 71 5265267
e-mail: boroep@lumc.nl

Abstract

We previously reported that a disparate distribution between killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) class 1 genes is associated with susceptibility to develop type 1 diabetes. Here we compare multiple models which reflect the combined genotype effects of combinations of functional inhibitory and activating KIRs in relation to HLA in an extended cohort of patients with juvenile-onset type 1 diabetes and non-diabetic control subjects. Our results suggest that autoimmunity in type 1 diabetes is mainly associated with a decrease in inhibitory KIRHLA genotype combinations, while the influence of activating KIR genotypes seems redundant. However, logistic regression showed that activating KIR genotypes do influence the overall hierarchy of protection/susceptibility as reflected by composite inhibitory and activating KIRHLA genotype models.

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