Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers

A. M. Hughes, P. Jokinen, Danika L Bannasch, H. Lohi, A. M. Oberbauer

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Canine hypoadrenocorticism (Addison's disease) is due to a deficiency of corticosteroids and mineralocorticoids produced by the adrenals. Although this is a relatively uncommon disease in the general dog population, some breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR), are at increased risk for developing hypoadrenocorticism. A prior study has shown that the increased risk is due to a heritable component. This potentially lethal disorder is hypothesized to have an autoimmune etiology, thus the aim of this study was to determine whether genetic susceptibility to hypoadrenocorticism in NSDTRs is associated with genes of the canine major histocompatibility complex [MHC; dog leukocyte antigen system (DLA)]. Samples were collected from NSDTRs diagnosed with hypoadrenocorticism and healthy siblings or country-matched controls. The DLA class II alleles and haplotypes were determined and compared between cases and controls. We found seven different haplotypes of which the haplotype DLA-DRB1*01502/DQA*00601/DQB1*02301 was significantly more prevalent in the diseased dogs (P = 0.044). In addition, these affected dogs also were more likely to be homozygous across the DLA class II region than the control dogs (OR = 6.7, CI = 1.5-29.3, P = 0.011). We also found that homozygous dogs, regardless of their haplotype, tended to have earlier disease onset compared with heterozygous dogs. These data indicate a limited MHC diversity in North American NSDTRs and suggest that the MHC may play a role in the development of hypoadrenocorticism in the NSDTR, supporting the autoimmune origin of the disease.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalTissue Antigens
Volume75
Issue number6
DOIs
StatePublished - 2010

Fingerprint

Nova Scotia
Ducks
HLA Antigens
Haplotypes
Dogs
Canidae
Dog Diseases
Addison Disease
Mineralocorticoids
Genetic Predisposition to Disease
Major Histocompatibility Complex
Autoimmune Diseases
Adrenal Cortex Hormones
Alleles

Keywords

  • Addison's disease
  • Canine
  • Dog leukocyte antigen
  • Hypoadrenocorticism
  • Immune mediated
  • Nova Scotia Duck Tolling Retriever

ASJC Scopus subject areas

  • Immunology and Allergy
  • Genetics
  • Immunology
  • Medicine(all)

Cite this

Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers. / Hughes, A. M.; Jokinen, P.; Bannasch, Danika L; Lohi, H.; Oberbauer, A. M.

In: Tissue Antigens, Vol. 75, No. 6, 2010, p. 684-690.

Research output: Contribution to journalArticle

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abstract = "Canine hypoadrenocorticism (Addison's disease) is due to a deficiency of corticosteroids and mineralocorticoids produced by the adrenals. Although this is a relatively uncommon disease in the general dog population, some breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR), are at increased risk for developing hypoadrenocorticism. A prior study has shown that the increased risk is due to a heritable component. This potentially lethal disorder is hypothesized to have an autoimmune etiology, thus the aim of this study was to determine whether genetic susceptibility to hypoadrenocorticism in NSDTRs is associated with genes of the canine major histocompatibility complex [MHC; dog leukocyte antigen system (DLA)]. Samples were collected from NSDTRs diagnosed with hypoadrenocorticism and healthy siblings or country-matched controls. The DLA class II alleles and haplotypes were determined and compared between cases and controls. We found seven different haplotypes of which the haplotype DLA-DRB1*01502/DQA*00601/DQB1*02301 was significantly more prevalent in the diseased dogs (P = 0.044). In addition, these affected dogs also were more likely to be homozygous across the DLA class II region than the control dogs (OR = 6.7, CI = 1.5-29.3, P = 0.011). We also found that homozygous dogs, regardless of their haplotype, tended to have earlier disease onset compared with heterozygous dogs. These data indicate a limited MHC diversity in North American NSDTRs and suggest that the MHC may play a role in the development of hypoadrenocorticism in the NSDTR, supporting the autoimmune origin of the disease.",
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