Systematic Review and Meta-Analysis of Candidate Gene Association Studies With Fracture Risk in Physically Active Participants

Edward Ryan-Moore,Yiannis Mavrommatis,Mark Waldron

doi:10.3389/fgene.2020.00551

Edward Ryan-Moore, Yiannis Mavrommatis + Show 1 more

Open Access

https://doi.org/10.3389/fgene.2020.00551

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Abstract

Background: Fractures are common in physically active populations and genetic differences may mediate injury risk.Objective: To meta-analyse the pooled results of candidate gene association studies with non-osteoporotic fracture risk in physically active humans.Methods: Systematic searching of databases returned 11 eligible studies published in English. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were produced using allele contrast, recessive and homozygote contrast meta-analysis models to evaluate associations of risk alleles in the COL1A1 (rs1800012), COL2A1 (rs412777), CTR (rs1801197), ESR1 (rs2234693 and rs9340799) LRP5 (rs3736228), VDR (rs10735810, rs7975232, rs1544410, and rs731236) genes with fracture incidence.Results: Eligible study quality was generally low (7/11) and no significant overall effect was found for any genetic variant with any comparison model (p > 0.05). A trivial reduction in fracture risk was found for female participants with the COL1A1 Sp1 (rs1800012) T allele (OR = 0.48, 95% CI = 0.25–0.91, p = 0.03, d = –0.18).Conclusions: No overall effect was found from the pooled results of included genetic variants on fracture risk in physically active participants. The COL1A1 Sp1 rs1800012 T allele may reduce fracture risk in physically active females but further high-quality research with sex-specific analysis is required.Trial Registration: (PROSPERO; CRD42018115008).

Highlights

Fractures are major musculoskeletal injuries, accounting for 22% of all sport and recreation related injuries in the United States (Conn et al, 2003)
Physical activity provides an important stimulus for bone health and is recommended to protect against osteoporotic fracture (Kohrt et al, 2004)
Exclusion of poor-quality studies reduced the analysis to two genetic variants in two different genes (COL1A1 rs1800012 and vitamin D receptor (VDR) rs1544410) from three studies, but this did not change the overall effect in these analyses. The aim of this meta-analysis was to evaluate the findings of candidate gene association studies on non-osteoporotic fracture risk in physically active humans

Summary

Introduction

Fractures are major musculoskeletal injuries, accounting for 22% of all sport and recreation related injuries in the United States (Conn et al, 2003). SNPs in the collagen type 1 alpha 1 (COL1A1), vitamin D receptor (VDR), and LDL receptor related protein 5 (LRP5) genes have been associated with a three- to eight-fold increase of fracture risk among physically active participants in some studies (Chatzipapas et al, 2009; Blades et al, 2010; Korvala et al, 2010), yet others have shown no association with the same SNPs (Cosman et al, 2013; Varley et al, 2018). Combining physically active male and female participants in genetic association with fracture risk may contribute to the inconsistency observed across studies. Objective: To meta-analyse the pooled results of candidate gene association studies with non-osteoporotic fracture risk in physically active humans. The COL1A1 Sp1 rs1800012 T allele may reduce fracture risk in physically active females but further high-quality research with sex-specific analysis is required

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