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

Varley, I ORCID: 0000-0002-3607-8921, Greeves, JP, Sale, C ORCID: 0000-0002-5816-4169, Friedman, E, Moran, DS, Yanovich, R, Wilson, PJ, Gartland, A, Hughes, DC, Stellingwerff, T, Ranson, C, Fraser, WD and Gallagher, JA, 2016. Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury. Purinergic Signalling. ISSN 1573-9538

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Context: 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.
Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes.
Methods: In 210 Israeli Defence 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 Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies.
Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while 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).
Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury.

Item Type: Journal article
Publication Title: Purinergic Signalling
Creators: Varley, I., Greeves, J.P., Sale, C., Friedman, E., Moran, D.S., Yanovich, R., Wilson, P.J., Gartland, A., Hughes, D.C., Stellingwerff, T., Ranson, C., Fraser, W.D. and Gallagher, J.A.
Publisher: Springer
Date: 2016
ISSN: 1573-9538
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 04 Feb 2016 13:43
Last Modified: 09 Jun 2017 13:58

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