Tully L J, Murphy A M, Smith R K W, Hulin-Curtis S L, Verheyen K L P, Price J S
Royal Veterinary College, London, UK.
Equine Vet J. 2014 May;46(3):289-93. doi: 10.1111/evj.12134. Epub 2013 Sep 16.
To explore whether genetic susceptibility is a potential risk factor for superficial digital flexor (SDF) tendinopathy in Thoroughbred (TB) racehorses.
To identify informative single nucleotide polymorphisms (SNPs) that capture genetic diversity across a range of candidate genes and to investigate, in a case-control study, their association with SDF tendinopathy in UK National Hunt TB racehorses in training.
Case-control candidate gene association study.
This study used in silico gene assembly and DNA sequencing to screen candidate genes for SNPs. Seven candidate genes were selected using a hypothesis-driven approach: tenascin-C (TNC), collagen, type 1, α 1 (COL1A1), collagen, type 5, α 1 (COL5A1), matrix metalloproteinase type 3 (MMP3), matrix metalloproteinase type 13 (MMP13), fibromodulin (FMOD) and cartilage oligomeric matrix protein (COMP). The SNPs were validated in DNA isolated from 48 TB racehorses and used to genotype 270 racehorses with SDF tendinopathy and 270 yard-matched controls. Genotyping of cases and controls was performed using SNaPshot™.
Racehorses heterozygous for the TNC BIEC2-696469 polymorphism were less likely to have SDF tendinopathy than racehorses homozygous for the wild-type allele (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.36-0.85, P = 0.01). This finding remained significant after adjustment for age and racing background (OR 0.57, 95% CI 0.36-0.92, P = 0.03). Racehorses homozygous for the novel COL5A1 COL5A1_01 variant allele were nearly 3 times more likely to have SDF tendinopathy than those homozygous for the wild-type allele (OR 2.82, 95% CI 1.25-6.35, P = 0.01); this association remained significant after adjustment for age and racing background (OR 2.77, 95% CI 1.18-6.53, P = 0.03).
Results suggest that sequence variants in TNC and COL5A1 genes are associated with SDF tendinopathy in TB racehorses. In future genetic markers may be used to identify horses at risk of SDF tendinopathy.
探讨基因易感性是否为纯种赛马浅表趾浅屈肌腱病（SDF）的潜在风险因素。
识别能反映一系列候选基因遗传多样性的信息性单核苷酸多态性（SNP），并在一项病例对照研究中调查其与英国国家障碍赛中正在训练的纯种赛马SDF肌腱病的关联。
病例对照候选基因关联研究。
本研究采用电子基因组装和DNA测序来筛选候选基因中的SNP。采用假设驱动的方法选择了7个候选基因：腱生蛋白-C（TNC）、Ⅰ型胶原α1链（COL1A1）、Ⅴ型胶原α1链（COL5A1）、基质金属蛋白酶3型（MMP3）、基质金属蛋白酶13型（MMP13）、纤维调节蛋白（FMOD）和软骨寡聚基质蛋白（COMP）。在从48匹纯种赛马分离的DNA中对SNP进行验证，并用于对270匹患有SDF肌腱病的赛马和270匹场地匹配的对照赛马进行基因分型。使用SNaPshot™对病例和对照进行基因分型。
TNC BIEC2 - 696469多态性的杂合子赛马比野生型等位基因纯合子赛马患SDF肌腱病的可能性更小（优势比[OR]0.56，95%置信区间[CI]0.36 - 0.85，P = 0.01）。在对年龄和比赛背景进行调整后，这一发现仍然显著（OR 0.57，95% CI 0.36 - 0.92，P = 0.03）。新型COL5A1 COL5A1_01变异等位基因纯合子赛马患SDF肌腱病的可能性比野生型等位基因纯合子赛马高近3倍（OR 2.82，95% CI 1.25 - 6.35，P = 0.01）；在对年龄和比赛背景进行调整后，这种关联仍然显著（OR 2.77，95% CI 1.18 - 6.53，P = 0.03）。
结果表明，TNC和COL5A1基因中的序列变异与纯种赛马的SDF肌腱病有关。未来，基因标记可能用于识别有SDF肌腱病风险的马匹。
