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Association of Doberman hepatitis to canine major histocompatibility complex II

Authors

  • H. Dyggve,

    Corresponding author
    1. Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
    2. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland
    3. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
      Hanna Dyggve, DVM
      Department of Equine and Small Animal Medicine
      PO Box 57
      00014 University of Helsinki
      Helsinki
      Finland
      Tel: +358 50 3572657
      Fax: +358919157381
      e-mail: hanna.dyggve@gmail.com
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  • L. J. Kennedy,

    1. Centre for Integrated Genomic Research, University of Manchester, Manchester, UK
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  • S. Meri,

    1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland
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  • T. Spillmann,

    1. Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
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  • H. Lohi,

    1. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
    3. Folkhälsan Institute of Genetics, Helsinki, Helsinki, Finland
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    • These authors contributed equally to this work.

  • M. Speeti

    1. Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
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    • These authors contributed equally to this work.


Hanna Dyggve, DVM
Department of Equine and Small Animal Medicine
PO Box 57
00014 University of Helsinki
Helsinki
Finland
Tel: +358 50 3572657
Fax: +358919157381
e-mail: hanna.dyggve@gmail.com

Abstract

Doberman hepatitis (DH) is a chronic and progressive inflammatory liver disease that mainly affects female dogs. The high incidence of chronic hepatitis in Dobermans is suggestive of a genetic predisposition. DH is characterized by mononuclear cell infiltration and copper accumulation in the liver and major histocompatibility complex (MHC) class II antigen expression in the hepatocytes. In dogs, the MHC is referred to as the dog leukocyte antigen (DLA) system. In this study, the potential role of DLA genes in DH was investigated by sequence-based typing in the exon 2 of DLA-DRB1, -DQA1 and -DQB1. The case group comprised 37 Dobermans with subclinical or clinical DH. The control group consisted of 37 healthy Dobermans, with normal liver enzyme values and without immunosuppressive medication. The control dogs were over 10 years old to include dogs with the lowest genetic risk of DH. Our results indicate that Dobermans with homozygous DLA-DRB1*00601/DQA1*00401/DQB1*01303 [odds ratio (OR) = 14.9, confidence limit (CL) = 3.1–71.7, P < 0.00005], especially with homozygosity for DLA-DRB1*00601 (P < 0.0005), are susceptible to DH. The DQ heterodimer DLA-DQA1*00901/DQB1*00101 and the allele DLA-DRB1*01501 appear to confer protection against DH (P < 0.001). Allele and haplotype frequencies were compared using chi-squared statistics. The disease shows a complex pattern of inheritance, but the observed DLA class II association with DH suggests a role for the immune system in the development of the disease.

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