Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

Alisdair Boag; Andrea Short; Lorna J Kennedy; Hattie  Syme; Peter Graham; Brian Catchpole

doi:10.1186/s40575-020-0081-4

Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

Alisdair Boag
, Andrea Short
, Lorna J Kennedy
, Hattie Syme
, Peter Graham
, Brian Catchpole

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

Abstract

Background:
Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison’s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT).

Results:
Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites.

Conclusions:
This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.

Original language	English
Journal	Canine Medicine and Genetics
DOIs	https://doi.org/10.1186/s40575-020-0081-4
Publication status	Published - 4 Mar 2020

Keywords / Materials (for Non-textual outputs)

Addison’s, Canine
CTLA-4
Hypoadrenocorticism
Promoter

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10.1186/s40575-020-0081-4

Boag2020_Article_PolymorphismsInTheCTLA4Promote
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Final published version, 1.23 MBLicence: Creative Commons: Attribution (CC-BY)

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@article{481b66bd47ed4344938931d7907442bc,

title = "Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism",

abstract = "Background: Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison{\textquoteright}s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT). Results: Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites. Conclusions: This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism. ",

keywords = "Addison{\textquoteright}s, Canine, CTLA-4, Hypoadrenocorticism, Promoter",

author = "Alisdair Boag and Andrea Short and Kennedy, \{Lorna J\} and Hattie Syme and Peter Graham and Brian Catchpole",

year = "2020",

month = mar,

day = "4",

doi = "10.1186/s40575-020-0081-4",

language = "English",

journal = "Canine Medicine and Genetics",

issn = "2662-9380",

publisher = "BMC",

}

TY - JOUR

T1 - Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

AU - Boag, Alisdair

AU - Short, Andrea

AU - Kennedy, Lorna J

AU - Syme, Hattie

AU - Graham, Peter

AU - Catchpole, Brian

PY - 2020/3/4

Y1 - 2020/3/4

N2 - Background: Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison’s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT). Results: Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites. Conclusions: This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.

AB - Background: Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison’s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT). Results: Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites. Conclusions: This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.

KW - Addison’s, Canine

KW - CTLA-4

KW - Hypoadrenocorticism

KW - Promoter

U2 - 10.1186/s40575-020-0081-4

DO - 10.1186/s40575-020-0081-4

M3 - Article

SN - 2662-9380

JO - Canine Medicine and Genetics

JF - Canine Medicine and Genetics

ER -

Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

Abstract

Keywords / Materials (for Non-textual outputs)

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