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.
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DOI：
10.1186/s40575-020-00093-9
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发表时间：
2020-10-31
影响因子：
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通讯作者：
Kennedy LJ
中科院分区：
文献类型：
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作者：
Denyer AL;Massey JP;Davison LJ;Ollier WER;Catchpole B;Kennedy LJ
犬糖尿病（CanineDiabetesMellitus，DM）是家犬常见的内分泌疾病。许多病理学机制被认为有助于相对或绝对胰岛素缺乏症的病因学，包括免疫介导的胰腺β细胞破坏。糖尿病的风险在不同的狗品种之间有很大的差异，这表明遗传因素参与其中，并有助于易感性或保护。特定的犬白细胞抗原（DLA）II类单倍型与DM的关联已被确定，但迄今为止的调查仅考虑所有品种合并在一起。本研究的目的是分析一个扩展的数据集，以确定品种特异性糖尿病相关的DLA单倍型。选择英国犬糖尿病登记册中最具代表性的12个品种进行研究。分析了来自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，以使DLA的品种特异性分析成为可能。使用基于DNA序列的分型对犬进行DLA-DRB 1、-DQA 1、-DQB 1基因座的等位基因变异的基因分型。从所有三个位点的基因型相结合，揭示三个位点的DLA II类单倍型，这与DM的统计学关联进行了评估。这是对每个品种单独进行的，也是对所有品种合并进行的。5个犬种被鉴定为具有一个或多个与DM易感性或保护相关的DLA单倍型。四个DM相关的单倍型被确定在可卡犬品种，其中一个单倍型与边境梗共享。在研究中包括的三个已知的糖尿病风险最高的品种（萨摩耶，西藏梗和凯恩梗）中，没有发现DLA单倍型与糖尿病相关。新的DLA协会与糖尿病在特定的狗品种提供了进一步的证据表明，免疫反应基因有助于在某些情况下，这种疾病的易感性。同样明显的是，DLA可能不会对某些品种的DM造成明显或强烈的风险，包括分析的7个品种，未发现相关性。
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.