Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.
Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.
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DOI：
10.1371/journal.pone.0056490
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kennedy LJ
中科院分区：
文献类型：
--
作者：
Massey J;Rothwell S;Rusbridge C;Tauro A;Addicott D;Chinoy H;Cooper RG;Ollier WE;Kennedy LJ
一个品种特异性多发性肌炎是经常观察到在匈牙利维兹拉。已证明对免疫抑制治疗的有益临床应答，这表明免疫介导的病因学。犬炎性肌病与人类免疫介导的肌病具有临床和组织学相似性。由于MHC II类协会已报告在人类的条件下，我们调查是否MHC II类协会是目前在犬肌病看到在这个品种。对212只匈牙利Vizsla系谱犬根据疾病状态和与患病犬的相关程度进行分层。这产生了一组29个病例和183个“分级”对照：93个未受影响的狗与一级受影响的亲属，44个未受影响的狗与二级受影响的亲属，和46个未受影响的狗没有已知的受影响的亲属。鉴定出11种DLA II类单倍型，其中DLA-DRB 1 *02001/DQA 1 *00401/DQB 1 *01303在病例组中的频率显著高于对照组（OR = 1.92，p = 0.032）。 当仅将无疾病家族史的对照犬与病例进行比较时，这种关联进一步加强（OR = 4.08，p = 0.00011）。 此外，风险单倍型的单个拷贝足以增加疾病风险，纯合子的风险大幅增加。随着相关程度的增加，该单倍型的频率有增加的趋势，表明疾病外显率较低。这些研究结果支持免疫介导的病因学的假设，这种犬肌病，并提供可信度，可能使用匈牙利Vizsla作为与人类肌炎比较研究的遗传模型。
A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 “graded” controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.
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影响因子：
9.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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