DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs

Research output: Contribution to journalArticle

Abstract

Addison’s disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x 2 p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x 2 p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x 2 p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.

Original languageEnglish (US)
Pages (from-to)373-382
Number of pages10
JournalImmunogenetics
Volume71
Issue number5-6
DOIs
StatePublished - May 1 2019

Fingerprint

Addison Disease
Haplotypes
Dogs
Population
MHC Class II Genes
Exons
Alleles

Keywords

  • Autoimmune disease
  • Canine
  • DLA
  • Hypoadrenocorticism
  • Major histocompatibility complex class II

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs. / Treeful, Amy E.; Rendahl, Aaron K.; Friedenberg, Steven G.

In: Immunogenetics, Vol. 71, No. 5-6, 01.05.2019, p. 373-382.

Research output: Contribution to journalArticle

@article{bd6ddf5a5e914e51a0d5cab38ec8f202,
title = "DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs",
abstract = "Addison’s disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x 2 p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x 2 p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x 2 p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.",
keywords = "Autoimmune disease, Canine, DLA, Hypoadrenocorticism, Major histocompatibility complex class II",
author = "Treeful, {Amy E.} and Rendahl, {Aaron K.} and Friedenberg, {Steven G.}",
year = "2019",
month = "5",
day = "1",
doi = "10.1007/s00251-019-01113-0",
language = "English (US)",
volume = "71",
pages = "373--382",
journal = "Immunogenetics",
issn = "0093-7711",
publisher = "Springer Verlag",
number = "5-6",

}

TY - JOUR

T1 - DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs

AU - Treeful, Amy E.

AU - Rendahl, Aaron K.

AU - Friedenberg, Steven G.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Addison’s disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x 2 p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x 2 p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x 2 p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.

AB - Addison’s disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x 2 p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x 2 p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x 2 p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.

KW - Autoimmune disease

KW - Canine

KW - DLA

KW - Hypoadrenocorticism

KW - Major histocompatibility complex class II

UR - http://www.scopus.com/inward/record.url?scp=85065894722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065894722&partnerID=8YFLogxK

U2 - 10.1007/s00251-019-01113-0

DO - 10.1007/s00251-019-01113-0

M3 - Article

VL - 71

SP - 373

EP - 382

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

IS - 5-6

ER -