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Title: Association of genotype with bone metabolism, skeletal adaptation and stress fracture injury occurrence
Author: Varley, I.
ISNI:       0000 0004 5353 0988
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2014
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Positive changes in bone metabolism, structural characteristics, size and mass are commonly associated with weight-bearing exercise. Despite this, negative effects of exercise on bone phenotypes, such as stress fracture injuries have been reported. Little is known about the extent of the genetic mediation of changes in bone characteristics, stress fracture injury and bone resorption in response to exercise. Accordingly, this thesis investigated: the genotype dependent changes in bone phenotypes in academy footballers before and after an increase in training volume; genetic associations with stress fracture injury in elite athletes and a preliminary investigation into genetic associations with bone resorption following 120 min of treadmill running. The tibial bone characteristics of 80, full-time academy footballers was determined using pQCT before and after 12 weeks of increased volume football training. Genetic associations with baseline, post increased training and change in bone characteristics were then determined. Secondly, radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Genetic associations were analysed for the whole group, and were also sub-stratified. Finally, recreationally active healthy male participants (n=42) performed a 120 min run at 70% O2max. Genetic associations with bone resorption at baseline, immediately, 24, 48 and 72 hours post run were investigated. SNPs in the proximity of genes in P2X7R and the RANK/RANKL/OPG signalling and Wnt signalling pathways were associated with bone phenotypes before and following 12 weeks of increased volume football training (P<0.05). SNPs in close proximity to SOST, P2X7R, RANK, RANKL, OPG, Bradykinin and VDR genes were associated with stress fracture injury in the whole cohort and in various sub-classifications of elite athletes (P<0.05). No associations were shown in bone resorption prior to, immediately following or in the 3 days following 120 min of treadmill running. The data suggest a role for specific genes and SNPs in bone phenotypic changes as a result of exercise training and in the susceptibility to stress fracture injury. The association of SNPs in P2X7R and the RANK/RANKL/OPG signalling and Wnt signalling pathways with bone phenotypes and stress fracture injury susceptibility highlights their role in the maintenance of bone health, and offers potential targets for therapeutic interventions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available