Denyer A L, Massey J P, Davison L J, Ollier W E R, Catchpole B, Kennedy L J
Department of Pathology and Pathogen Biology, Royal Veterinary College, Hatfield, UK.
Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
Canine Med Genet. 2020 Oct 31;7(1):15. doi: 10.1186/s40575-020-00093-9.
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.
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.
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.
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.
犬糖尿病（DM）是家犬中一种常见的内分泌疾病。许多病理机制被认为与相对或绝对胰岛素缺乏的病因发病机制有关，包括胰腺β细胞的免疫介导破坏。不同犬种之间的糖尿病风险差异很大，这表明遗传因素参与其中并导致易感性或保护性。已经确定了特定犬白细胞抗原（DLA）II类单倍型与糖尿病的关联，但迄今为止的研究仅考虑了所有犬种合并在一起的情况。本研究的目的是分析一个扩展的数据集，以确定特定品种与糖尿病相关的DLA单倍型。
选择英国犬糖尿病登记册中代表度最高的12个犬种进行研究。分析了646只糖尿病犬和912只品种匹配的非糖尿病对照犬的DLA分型数据，以便对DLA进行特定品种分析。使用基于DNA序列的分型方法对犬在DLA-DRB1、-DQA1、-DQB1位点的等位基因变异进行基因分型。将来自所有三个位点的基因型组合起来，以揭示三位点DLA II类单倍型，并评估其与糖尿病的统计学关联。这分别针对每个品种以及所有品种合并在一起进行。
确定了五个犬种具有一种或多种与糖尿病易感性或保护性相关的DLA单倍型。在可卡犬品种中鉴定出四种与糖尿病相关的单倍型，其中一种单倍型与边境梗犬共有。在本研究中已知糖尿病风险最高的三个犬种（萨摩耶犬、西藏梗犬和凯恩梗犬）中，未发现与糖尿病相关的DLA单倍型。
特定犬种中DLA与糖尿病的新关联进一步证明，免疫反应基因在某些情况下会导致对这种疾病的易感性。同样明显的是，DLA可能在某些品种中对糖尿病没有明显或强烈的风险贡献，包括分析的七个未发现关联的品种。
