Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy: Role for Angiogenesis-Associated Genes

Masouda Rahim, Louis Y El Khoury, Stuart M Raleigh, William J Ribbans, Michael Posthumus, Malcolm Collins, Alison V September

Research output: Contribution to journalArticle

9 Citations (Scopus)
38 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)520-527
Number of pages8
JournalOmics : a journal of integrative biology
Volume20
Issue number9
Early online date1 Sep 2016
DOIs
Publication statusPublished - Sep 2016
Externally publishedYes

Fingerprint

Tendinopathy
Sports Medicine
Tendons
Medical Genetics
Sports
Vascular Endothelial Growth Factor A
Medicine
South Africa
Protein Isoforms
Genes
Tendon Injuries
Vascular Endothelial Growth Factor Receptor-2
Fibroblasts
Polymorphism
Stretching
Throughput
Health
Cytokines
Precision Medicine
Metabolomics

Bibliographical note

Final publication is available from Mary Ann Liebert, Inc., publishers: http://dx.doi.org/10.1089/omi.2016.0116.

Keywords

  • Achilles Tendon
  • Adult
  • Anterior Cruciate Ligament Injuries
  • European Continental Ancestry Group
  • Female
  • Gene Frequency
  • Genetic Variation
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Physiologic
  • Polymorphism, Single Nucleotide
  • Risk
  • South Africa
  • Sports Medicine
  • Tendinopathy
  • United Kingdom
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • Journal Article

Cite this

Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy : Role for Angiogenesis-Associated Genes. / Rahim, Masouda; El Khoury, Louis Y; Raleigh, Stuart M; Ribbans, William J; Posthumus, Michael; Collins, Malcolm; September, Alison V.

In: Omics : a journal of integrative biology, Vol. 20, No. 9, 09.2016, p. 520-527.

Research output: Contribution to journalArticle

Rahim, Masouda ; El Khoury, Louis Y ; Raleigh, Stuart M ; Ribbans, William J ; Posthumus, Michael ; Collins, Malcolm ; September, Alison V. / Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy : Role for Angiogenesis-Associated Genes. In: Omics : a journal of integrative biology. 2016 ; Vol. 20, No. 9. pp. 520-527.
@article{c2587218525145a2bb5c4f0c5c1fc5be,
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.",
keywords = "Achilles Tendon, Adult, Anterior Cruciate Ligament Injuries, European Continental Ancestry Group, Female, Gene Frequency, Genetic Variation, Haplotypes, Humans, Male, Middle Aged, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Risk, South Africa, Sports Medicine, Tendinopathy, United Kingdom, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, Journal Article",
author = "Masouda Rahim and {El Khoury}, {Louis Y} and Raleigh, {Stuart M} and Ribbans, {William J} and Michael Posthumus and Malcolm Collins and September, {Alison V}",
note = "Final publication is available from Mary Ann Liebert, Inc., publishers: http://dx.doi.org/10.1089/omi.2016.0116.",
year = "2016",
month = "9",
doi = "10.1089/omi.2016.0116",
language = "English",
volume = "20",
pages = "520--527",
journal = "OMICS A Journal of Integrative Biology",
issn = "1536-2310",
publisher = "Mary Ann Liebert",
number = "9",

}

TY - JOUR

T1 - Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy

T2 - Role for Angiogenesis-Associated Genes

AU - Rahim, Masouda

AU - El Khoury, Louis Y

AU - Raleigh, Stuart M

AU - Ribbans, William J

AU - Posthumus, Michael

AU - Collins, Malcolm

AU - September, Alison V

N1 - Final publication is available from Mary Ann Liebert, Inc., publishers: http://dx.doi.org/10.1089/omi.2016.0116.

PY - 2016/9

Y1 - 2016/9

N2 - 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.

AB - 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.

KW - Achilles Tendon

KW - Adult

KW - Anterior Cruciate Ligament Injuries

KW - European Continental Ancestry Group

KW - Female

KW - Gene Frequency

KW - Genetic Variation

KW - Haplotypes

KW - Humans

KW - Male

KW - Middle Aged

KW - Neovascularization, Physiologic

KW - Polymorphism, Single Nucleotide

KW - Risk

KW - South Africa

KW - Sports Medicine

KW - Tendinopathy

KW - United Kingdom

KW - Vascular Endothelial Growth Factor A

KW - Vascular Endothelial Growth Factor Receptor-2

KW - Journal Article

U2 - 10.1089/omi.2016.0116

DO - 10.1089/omi.2016.0116

M3 - Article

VL - 20

SP - 520

EP - 527

JO - OMICS A Journal of Integrative Biology

JF - OMICS A Journal of Integrative Biology

SN - 1536-2310

IS - 9

ER -