SNPs in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt signalling pathways and their association with bone phenotypes in academy footballers

Ian Varley (Lead Author), David C. Hughes, Julie P. Greeves, William D. Fraser, Craig Sale

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Context: Genotype plays an important role in influencing bone phenotypes, such as bone mineral density, but the role of genotype in determining responses of bone to exercise has yet to be elucidated. 
Objective: To determine whether 10 SNPs associated with genes in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt Signalling Pathways are associated with bone phenotypes in elite academy footballers (Soccer players) and to determine whether these genotypes are associated with training induced changes in bone. 
Design, participants, and methods: 99 elite academy footballers volunteered to participate. Peripheral computed tomography of the tibia (4%, 14%, 38% and 66% sites) was performed immediately before and 12 weeks after an increase in football training volume. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. 
Results: No significant genotype by time interactions were shown for any of the SNPs analysed (P > .05). A main effect of genotype was shown. SOST SNP rs1877632 (trabecular density), P2X7R SNPs rs1718119 (cortical thickness and CSA), rs3751143 (SSI, CSA, cortical CSA and periosteal circumference) RANK/RANKL/OPG SNPs rs9594738 (periosteal circumference), rs1021188 (cortical thickness and CSA) and rs9594759 (cortical density) were associated with bone phenotypes (P < .05). 
Conclusions: No association was shown between P2X7R, RANK/RANKL/OPG and Wnt Signalling SNPs and a change in bone phenotypes following 12 weeks of increased training volume in elite academy footballers. However, SNPs were associated with bone phenotypes pre training. These data highlight the complexity of the interaction between SNPs in the vicinity of the RANK/RANKL/OPG, P2X7R and Wnt metabolic regulatory pathways and bone phenotypes in elite academy footballers.
Original languageEnglish
Pages (from-to)179–185
Number of pages7
Early online date8 Jan 2018
Publication statusPublished - Mar 2018


  • Genetics
  • P2X7R
  • Wnt signalling
  • Exercise

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