title: Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy: Role for Angiogenesis-Associated Genes.
abstract: Sport and Exercise Medicine is one of the important subspecialties of 21st century healthcare contributing to improving the physical function, health, and vitality of populations while reducing the prevalence of lifestyle-related diseases. Moreover, sport and exercise are associated with injuries such as Achilles tendinopathy, which is a common tendon injury. The angiogenesis-associated signaling pathway plays a key role in extracellular matrix remodeling, with increased levels of angiogenic cytokines reported after cyclic stretching of tendon fibroblasts. We investigated the variants in angiogenesis genes in relation to the risk of Achilles tendinopathy in two population samples drawn independently from South Africa (SA) and the United Kingdom (UK). The study sample comprised 120 SA and 130 UK healthy controls, and 108 SA and 87 UK participants with Achilles tendinopathy. All participants were genotyped for five functional polymorphisms in the vascular endothelial growth factor, A isoform (VEGFA) (rs699947, rs1570360, rs2010963) and kinase insert-domain receptor (KDR) genes (rs1870377, rs2071559). The VEGFA A-G-G inferred haplotype was associated with an increased risk of Achilles tendinopathy in the SA group (15% in controls vs. 20% in cases, p = 0.048) and the combined SA+UK group (14% in controls vs. 20% in cases, p = 0.009). These new findings implicate the VEGFA gene with Achilles tendinopathy risk, while highlighting the potential biological significance of the angiogenesis signaling pathway in the etiology of Achilles tendinopathy. The evidence suggesting a genetic contribution to the susceptibility of sustaining a tendon injury is growing. We anticipate that high-throughput and multi-omics approaches, building on genomics, proteomics, and metabolomics, may soon uncover the pathophysiology of many diseases in the field of Sports and Exercise Medicine, as a new frontier of global precision medicine.
authors.affiliation: 1 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Masouda
authors.initials: M
authors.lastname: Rahim
authors.affiliation: 2 School of Biological Sciences, University of Essex , Colchester, United Kingdom .
authors.forename: Louis Y
authors.initials: LY
authors.lastname: El Khoury
authors.affiliation: 3 Division of Health and Life Sciences, Centre for Physical Activity and Chronic Disease, Institute of Health and Wellbeing, University of Northampton , Northampton, United Kingdom .
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Raleigh
authors.affiliation: 3 Division of Health and Life Sciences, Centre for Physical Activity and Chronic Disease, Institute of Health and Wellbeing, University of Northampton , Northampton, United Kingdom .
authors.forename: William J
authors.initials: WJ
authors.lastname: Ribbans
authors.affiliation: 1 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Michael
authors.initials: M
authors.lastname: Posthumus
authors.affiliation: 1 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Malcolm
authors.initials: M
authors.lastname: Collins
authors.affiliation: 1 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Alison V
authors.initials: AV
authors.lastname: September
mesh_terms: D000125:Achilles Tendon / Q000503:physiopathology; D000328:Adult; D000070598:Anterior Cruciate Ligament Injuries / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D013019:South Africa; D013178:Sports Medicine; D052256:Tendinopathy / Q000235:genetics* / Q000503:physiopathology; D006113:United Kingdom; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D044465:White People
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2