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Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

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Abstract

Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. The aim of this study is to evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. In 210 Israeli Defense Forces (IDF) military conscripts, stress fracture injury was diagnosed (n = 43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n = 125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson’s chi-squared (χ 2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. The variant allele of P2X7R SNP rs3751143 (Glu496Ala—loss of function) was associated with stress fracture injury, whilst the variant allele of rs1718119 (Ala348Thr—gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P < 0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P < 0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P < 0.05). The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury.

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Acknowledgments

We are grateful to all participants for taking part in the study.

Disclosure statement

The authors have nothing to disclose.

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Authors and Affiliations

  1. Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement Research Centre, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK

    Ian Varley, Craig Sale & David C. Hughes

  2. Department of Occupational Medicine, Headquarters Army Recruiting and Training Division, Trenchard Lines, Upavon, Pewsey, Wilts SN9 6BE, UK

    Julie P. Greeves

  3. The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel

    Eitan Friedman

  4. Ariel and Heller Institue, Sheba Medical Center, Ariel University, Ramat Gen, Israel

    Daniel S. Moran & Ran Yanovich

  5. Bone and Joint Research Group, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Diseases, Faculty of Health and Life Sciences, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK

    Peter J. Wilson & James A. Gallagher

  6. The Mellanby Centre for Bone Research, Department of Human Metabolism, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Alison Gartland

  7. Canadian Sport Institute Pacific, Pacific Institute for Sport Excellence, Victoria, BC, V9E 2C5, Canada

    Trent Stellingwerff

  8. Cardiff School of Sport, Cardiff Metropolitan University, Cardiff, Wales, UK

    Craig Ranson

  9. Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK

    William D. Fraser

  10. Norfolk and Norwich University Hospital, Norfolk, NR4 7UY, UK

    William D. Fraser

Authors
  1. Ian Varley
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  2. Julie P. Greeves
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  3. Craig Sale
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  4. Eitan Friedman
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  5. Daniel S. Moran
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  6. Ran Yanovich
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  7. Peter J. Wilson
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  8. Alison Gartland
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  9. David C. Hughes
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  10. Trent Stellingwerff
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  11. Craig Ranson
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  12. William D. Fraser
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  13. James A. Gallagher
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Correspondence to Julie P. Greeves.

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Varley, I., Greeves, J.P., Sale, C. et al. Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury. Purinergic Signalling 12, 103–113 (2016). https://doi.org/10.1007/s11302-016-9495-6

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  • DOI: https://doi.org/10.1007/s11302-016-9495-6

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