Genetic Variants and Hamstring Injury in Soccer: an Association and Validation Study.

Purpose: To investigate the association of candidate single nucleotide polymorphisms (SNPs) with non-contact hamstring muscle injuries in elite soccer players, and to create and validate a model to assess the risk of hamstring injury. Methods: 107 elite male outfield players were prospectively followed for 6 seasons. Players were genotyped for 37 SNPs previously investigated in relation to musculoskeletal injuries. The association of SNPs, previous injury, age, level of play, position and anthropometric data with 129 hamstring injuries (413 observations) was investigated in the discovery phase (2010-2015), and a multivariable Cox-frailty model was created using forward selection. The model's discriminative ability was tested in the validation phase (2015-2016, 31 injuries, 98 observations) using Harrell's C index. Results: Five SNPs were found to be significantly associated with hamstring injury in a multivariable model, MMP3 (Matrix metalloproteinase-3) rs679620 (A vs. G, hazard ratio (HR)=2.06, 95% confidence interval (CI)=1.51-2.81), TNC (Tenascin-C) rs2104772 (A vs. T, HR=1.65, 95% CI=1.17-2.32), IL6 (Interleukin-6) rs1800795 (GG vs. GC+CC, HR=1.68, 95% CI=1.11-2.53), NOS3 (Nitric oxide synthase-3) rs1799983 (G vs. T, HR=1.35, 95% CI=1.01-1.79), and HIF1A (Hypoxia-inducible factor-1[alpha]) rs11549465 (CC vs. CT, HR=2.08, 95% CI=1.00-4.29). Age also entered the model (>=24 vs.

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