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

Larruskain, Jon; Celorrio, David; Barrio, Irantzu; Odriozola, Adrian; Gil, Susana M.; Fernandez-Lopez, Juan Ramon; Nozal, Raul; Ortuzar, Isusko; Lekue, Jose A.; Aznar, Jose M.
Medicine & Science in Sports & Exercise: Post Acceptance: October 02, 2017
doi: 10.1249/MSS.0000000000001434
Original Investigation: PDF Only

ABSTRACT

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-1α) rs11549465 (CC vs. CT, HR=2.08, 95% CI=1.00-4.29). Age also entered the model (≥24 vs. <24 years, HR=2.10, 95% CI=1.29-3.42). The model showed acceptable discrimination in the discovery phase (C index=0.74), but not in the validation phase (C index=0.52).

Conclusion

Genetic variants appear to be involved in the etiology of hamstring injuries, but were not found to have predictive value by themselves. Further research, increasing the number of genetic variants and including environmental factors in complex multifactorial risk models is necessary.

Corresponding author: Jose M. Aznar, PhD, Baigene, Lascaray Research Center, Avda. Miguel de Unamuno, 3, 01006 Vitoria-Gasteiz, Spain. Telephone: 00-34-696 081 961, Email: josem.aznaroviedo@gmail.com

The study was funded by Baigene. JL was supported by a PhD Studentship from the Vice-Chancellorship for Basque of the University of the Basque Country UPV/EHU (Euskararen arloko Errektoreordetza). IB acknowledges financial support from the Basque Government (IT620-13). SMG acknowledges financial support from the Basque Government (IT922-16) and the University of the Basque Country (PPG17/34). The study was funded by the genetics company Baigene. DC, JRFL, RN and JMA are members of Baigene. For the remaining authors none were declared. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

Accepted for Publication: 20 September 2017

© 2017 American College of Sports Medicine