Searching for "monogenic diabetes" in dogs using a candidate gene approach

Short, Andrea D.; Holder, Angela; Rothwell, Simon; Massey, Jonathan; Scholey, Rachel; Kennedy, L. J.; Catchpole, Briän; Ollier, William

doi:10.1186/2052-6687-1-8

Cited by 8 publications

(17 citation statements)

References 59 publications

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“…A large number of diabetes susceptibility genes, each contributing relatively small effects, have been identified in human T1D [ 19 ], Type 2 DM (T2D) [ 20 ] and monogenic DM [ 21 ]. This has prompted candidate gene studies in canine DM, which have largely focussed on T1D genes involved with immune function [ 22 – 25 ] and human monogenic diabetes genes [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Denyer

Massey

Davison

et al. 2020

Canine Genet Epidemiol

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Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes. Methods The 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs were genotyped for allelic variation at DLA-DRB1, -DQA1, -DQB1 loci using DNA sequence-based typing. Genotypes from all three loci were combined to reveal three-locus DLA class II haplotypes, which were evaluated for statistical associations with DM. This was performed for each breed individually and for all breeds pooled together. Results Five dog breeds were identified as having one or more DLA haplotype associated with DM susceptibility or protection. Four DM-associated haplotypes were identified in the Cocker Spaniel breed, of which one haplotype was shared with Border Terriers. In the three breeds known to be at highest risk of DM included in the study (Samoyed, Tibetan Terrier and Cairn Terrier), no DLA haplotypes were found to be associated with DM. Conclusions Novel DLA associations with DM in specific dog breeds provide further evidence that immune response genes contribute susceptibility to this disease in some cases. It is also apparent that DLA may not be contributing obvious or strong risk for DM in some breeds, including the seven breeds analysed for which no associations were identified.

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Section: Introductionmentioning

confidence: 99%

Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Denyer

Massey

Davison

et al. 2020

Canine Genet Epidemiol

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“…Additionally, Australian Terriers are known to be at risk for the disease in Sweden (Fall et al 2007). Two original studies have investigated the insulin ( INS ) gene region in dogs with diabetes and had a similar design that focused on a number of single-nucleotide polymorphisms (SNPs) within or near the INS gene in breed-matched diabetic cases and healthy control dogs (Short et al 2007, 2014). Both studies included Samoyeds but no Australian Terriers (Short et al 2007, 2014).…”

mentioning

confidence: 99%

“…Two original studies have investigated the insulin ( INS ) gene region in dogs with diabetes and had a similar design that focused on a number of single-nucleotide polymorphisms (SNPs) within or near the INS gene in breed-matched diabetic cases and healthy control dogs (Short et al 2007, 2014). Both studies included Samoyeds but no Australian Terriers (Short et al 2007, 2014). Two different INS variants were identified as protective against diabetes in Cocker Spaniels and Labrador Retrievers, one of these SNPs increased susceptibility to diabetes in Jack Russell Terriers, and a different INS variant increased the risk of diabetes in Cocker Spaniels (Short et al 2007, 2014).…”

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confidence: 99%

“…Both studies included Samoyeds but no Australian Terriers (Short et al 2007, 2014). Two different INS variants were identified as protective against diabetes in Cocker Spaniels and Labrador Retrievers, one of these SNPs increased susceptibility to diabetes in Jack Russell Terriers, and a different INS variant increased the risk of diabetes in Cocker Spaniels (Short et al 2007, 2014). Variation at the insulin-like growth factor 2 gene was found to be protective in Border Terriers (Short et al 2007).…”

mentioning

confidence: 99%

“…Variation at the insulin-like growth factor 2 gene was found to be protective in Border Terriers (Short et al 2007). These studies focused on SNPs within, or in close proximity to, a specific candidate gene of interest (mostly within 1.5 Kb of exon 1) (Short et al 2007, 2014). None of the above INS gene associations have been replicated in more than 1 breed and none have been reported in Samoyeds or Australian Terriers with diabetes.…”

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confidence: 99%

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An Exploratory Association Analysis of the Insulin Gene Region With Diabetes Mellitus in Two Dog Breeds

Hess

Henthorn

Devoto

et al. 2019

Journal of Heredity

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Samoyeds and Australian Terriers are the 2 dog breeds at highest risk (>10-fold) for diabetes mellitus in the United States. It is unknown if the insulin (INS) gene is involved in the pathophysiology of diabetes in Samoyeds and Australian Terriers. It was hypothesized that the INS gene region provides a common genetic causality for diabetes in Samoyeds and Australian Terriers. We conducted a 2-stage genetic association study involving both breeds. In the discovery stage (Stage 1), Samoyeds with and without diabetes were compared in the frequencies of 447 tagging single-nucleotide polymorphisms (SNPs) within 2.5 megabases (Mb) up- and downstream of the INS gene on the Illumina CanineHD BeadChip. SNPs yielding a P-value < 0.005 were selected for further follow-up. In the validation stage (Stage 2), Australian Terriers with and without diabetes were compared in the SNPs genotyped by the Affymetrix GeneChip Canine Genome 2.0 Array and within 1 Mb up- and downstream of the selected SNPs from Stage 1. Two SNPs that were in high linkage disequilibrium (LD, r2 = 0.7) were selected from Stage 1. In Stage 2, among the 76 SNPs examined, 5 were significantly associated with diabetes after Bonferroni’s correction for multiple comparisons. Three of these 5 SNPs were in complete LD (r2 = 1 for all associations) and the 2 remaining SNPs were in moderate LD (r2 = 0.4). In conclusion, an association between the INS gene region and diabetes was suggested in 2 dog breeds of different clades. This region could have importance in diabetes in other breeds or in canine diabetes at large.

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Assessment of glucocorticoid and antibiotic exposure as risk factors for diabetes mellitus in selected dog breeds attending UK primary‐care clinics

et al. 2023

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Background: Diabetes mellitus (DM) is an important endocrine disorder in dogs. This study explored prior exposure to glucocorticoids or antibiotic treatment as risk factors for developing DM in dogs attending primary-care VetCompass clinics in the UK. Methods: A breed frequency matched case-control study nested in a cohort of dogs (n = 480,469) aged 3 years or over was used to explore associations between glucocorticoid and antibiotic exposure and the odds of developing DM. Results: A total of 565 cases and 2179 controls were included. Dogs with DM had over four times the odds of exposure to glucocorticoids within 6 weeks prior to diagnosis (odds ratio [OR] 4.07, 95% confidence interval [CI] 2.41-6.89, p < 0.001) compared to controls within 6 weeks prior to a randomly selected quasi-date of diagnosis. Dogs that had only one unique documented antibiotic course had a decreased odds of developing DM (OR 0.65, 95% CI 0.46-0.91, p = 0.012) compared to dogs that had no documented courses of antibiotics.Limitations: This study only included selected breeds, so the results may not be generalisable to all dog breeds. Conclusions: Exposure to glucocorticoids is associated with a substantial increase in the risk of developing DM for the dog breeds included in this analysis.

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Searching for "monogenic diabetes" in dogs using a candidate gene approach

Cited by 8 publications

References 59 publications

Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

An Exploratory Association Analysis of the Insulin Gene Region With Diabetes Mellitus in Two Dog Breeds

Assessment of glucocorticoid and antibiotic exposure as risk factors for diabetes mellitus in selected dog breeds attending UK primary‐care clinics

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