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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01-29

AUTHORS

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

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 (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. More... »

PAGES

103-113

Journal

TITLE

Purinergic Signalling

ISSUE

1

VOLUME

12

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11302-016-9495-6

DOI

http://dx.doi.org/10.1007/s11302-016-9495-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012610722

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26825304


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32 schema:description 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.
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40 P2X7R gene
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42 Pearson's chi-squared test
43 SNPs
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46 alleles
47 association
48 athletes
49 bone remodelling
50 bone scan
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52 cases
53 chi-squared test
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56 competitive allele-specific PCR
57 conscripts
58 contribution
59 control
60 development
61 elite athletes
62 fracture cases
63 fracture control
64 fracture injuries
65 fracture predisposition
66 fracture prevalence
67 fractures
68 frequency
69 functional SNPs
70 functional polymorphisms
71 genes
72 genetic candidates
73 genetic predisposition
74 genotype frequencies
75 history
76 imaging scans
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85 occurrence
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87 personnel
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90 predisposition
91 prevalence
92 putative contribution
93 receptor gene
94 recruits
95 reduced occurrence
96 regulator
97 remodelling
98 role
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