Ian Varley1, David C Hughes2, Julie P Greeves3, Trent Stellingwerff4, Craig Ranson5, William D Fraser6, Craig Sale7. 1. Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement (SHAPE) Research Centre, School of Science and Technology, Nottingham Trent University, UK. 2. School of Health Sciences, Birmingham City University, City South Campus, UK. 3. Department of Occupational Medicine, Headquarters Army Recruiting and Training Division, UK. 4. Canadian Sport Institute Pacific, Pacific Institute for Sport Excellence, Canada. 5. Cardiff School of Sport, Cardiff Metropolitan University, UK. 6. Norwich Medical School, University of East Anglia, UK; Norfolk and Norwich University Hospital, UK. 7. Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement (SHAPE) Research Centre, School of Science and Technology, Nottingham Trent University, UK. Electronic address: craig.sale@ntu.ac.uk.
Abstract
OBJECTIVES: To determine, in conjunction with a wider investigation, whether 11 genetic variants in the vicinity of vitamin D, collagen and Wnt signalling pathways were associated with stress fracture injury in the Stress Fracture Elite Athlete (SFEA) cohort. DESIGN: Genotype-phenotype association study. METHODS: Self-reported stress fracture history and demographic data were recorded in 518 elite athletes, 449 male and 69 female (mean age 24.2±5.5 years) from the SFEA cohort. Elite athletes were assigned to two groups based on history of stress fracture injury. Data were analysed for the whole cohort and sub-stratified in to male only and multiple stress fracture cases. Genotype was determined using a proprietary fluorescence-based competitive allele-specific polymerase chain reaction assay. RESULTS: SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 were associated with stress fracture (p<0.05). In the whole cohort, rs1877632 heterozygotes and homozygotes of the rare allele combined made up 59% of stress fracture sufferers in comparison to 46% in the non-stress fracture group (p=0.05). In the multiple stress fracture cohort, homozygotes of the rare allele of rs10735810 and rs731236 showed an association with stress fracture when compared to those homozygotes for the common allele combined with heterozygotes (p=0.03; p=0.01). No significant associations were shown in the other SNPs analysed (p>0.05). CONCLUSIONS: These data suggest an important role for SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 in the pathophysiology of stress fracture. This might be due to the role of the SNPs in the regulation of bone remodelling and adaptation to mechanical loading, with potential implications for the prevention and treatment of stress fracture injuries.
OBJECTIVES: To determine, in conjunction with a wider investigation, whether 11 genetic variants in the vicinity of vitamin D, collagen and Wnt signalling pathways were associated with stress fracture injury in the Stress Fracture Elite Athlete (SFEA) cohort. DESIGN: Genotype-phenotype association study. METHODS: Self-reported stress fracture history and demographic data were recorded in 518 elite athletes, 449 male and 69 female (mean age 24.2±5.5 years) from the SFEA cohort. Elite athletes were assigned to two groups based on history of stress fracture injury. Data were analysed for the whole cohort and sub-stratified in to male only and multiple stress fracture cases. Genotype was determined using a proprietary fluorescence-based competitive allele-specific polymerase chain reaction assay. RESULTS: SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 were associated with stress fracture (p<0.05). In the whole cohort, rs1877632 heterozygotes and homozygotes of the rare allele combined made up 59% of stress fracture sufferers in comparison to 46% in the non-stress fracture group (p=0.05). In the multiple stress fracture cohort, homozygotes of the rare allele of rs10735810 and rs731236 showed an association with stress fracture when compared to those homozygotes for the common allele combined with heterozygotes (p=0.03; p=0.01). No significant associations were shown in the other SNPs analysed (p>0.05). CONCLUSIONS: These data suggest an important role for SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 in the pathophysiology of stress fracture. This might be due to the role of the SNPs in the regulation of bone remodelling and adaptation to mechanical loading, with potential implications for the prevention and treatment of stress fracture injuries.
Authors: Shawn D Flanagan; Kellen T Krajewski; Aaron M Sinnott; Caleb D Johnson; Shawn R Eagle; Alice D LaGoy; Meaghan E Beckner; Anne Z Beethe; Rose Turner; Mita T Lovalekar; Courtenay Dunn-Lewis; Chris Connaboy; Bradley C Nindl Journal: Syst Rev Date: 2018-12-23
Authors: Maciej Tarnowski; Patrycja Tomasiak; Marta Tkacz; Katarzyna Zgutka; Katarzyna Piotrowska Journal: Genes (Basel) Date: 2022-08-17 Impact factor: 4.141