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

Ian Varley, Julie P. Greeves*, Craig Sale, Eitan Friedman, Daniel S. Moran, Ran Yanovich, Peter J. Wilson, Alison Gartland, David C. Hughes, Trent Stellingwerff, Craig Ranson, William D. Fraser, James A. Gallagher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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 (χ2) 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.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalPurinergic Signalling
Issue number1
StatePublished - 1 Mar 2016
Externally publishedYes


  • Bone
  • P2X7 receptor
  • Stress fracture injury


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