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

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• 作者：Ian Varley ; Julie P. Greeves ; Craig Sale ; Eitan Friedman…
• 关键词：P2X7 receptor ; Bone ; Stress fracture injury
• 刊名：Purinergic Signalling
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：12
• 期：1
• 页码：103-113
• 全文大小：448 KB
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• 作者单位：Ian Varley (1)
  Julie P. Greeves (2)
  Craig Sale (1)
  Eitan Friedman (3)
  Daniel S. Moran (4)
  Ran Yanovich (4)
  Peter J. Wilson (5)
  Alison Gartland (6)
  David C. Hughes (1)
  Trent Stellingwerff (7)
  Craig Ranson (8)
  William D. Fraser (10) (9)
  James A. Gallagher (5)
  
  1. Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement Research Centre, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
  2. Department of Occupational Medicine, Headquarters Army Recruiting and Training Division, Trenchard Lines, Upavon, Pewsey, Wilts SN9 6BE, UK
  3. The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel
  4. Ariel and Heller Institue, Sheba Medical Center, Ariel University, Ramat Gen, Israel
  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
  6. The Mellanby Centre for Bone Research, Department of Human Metabolism, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK
  7. Canadian Sport Institute Pacific, Pacific Institute for Sport Excellence, Victoria, BC, V9E 2C5, Canada
  8. Cardiff School of Sport, Cardiff Metropolitan University, Cardiff, Wales, UK
  10. Norfolk and Norwich University Hospital, Norfolk, NR4 7UY, UK
  9. Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  Pharmacology and Toxicology
  Human Physiology
  Neurosciences
  Cancer Research
  
• 出版者：Springer Netherlands
• ISSN：1573-9546

文摘

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. Keywords P2X7 receptor Bone Stress fracture injury