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Reasons for performing the study To explore whether genetic susceptibility is a potential risk factor for superficial digital flexor (SDF) tendinopathy in Thoroughbred (TB) racehorses. Objectives 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. Study design Case–control candidate gene association study. Methods 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™. Results 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). Conclusions 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. |
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