Type I Collagen α1 Sp1 Polymorphism and the Risk of Cruciate Ligament Ruptures or Shoulder Dislocations

Khoschnau, Shwan; Melhus, Håkan; Jacobson, Annica; Rahme, Hans; Bengtsson, Henrik; Ribom, Eva; Grundberg, Elin; Mallmin, Hans; Michaëlsson, Karl

doi:10.1177/0363546508320805

Cited by 123 publications

(144 citation statements)

References 36 publications

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“…Since the previous ACL retreat, a growing number of common DNA sequence variants within genes involved in various biological processes have been associated with susceptibility to ACL rupture. These include variants within several genes that encode collagens [169][170][171][172][173][174][175] and proteoglycans 176 involved in the formation of the collagen fibril, the basic building block of ligaments. A subset of these variants has been specifically associated with ACL ruptures in females but not in males.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

“…For example, the functional Sp1-binding site polymorphism (rs1800012, G/T) within the COL1A1 gene is associated with ACL rupture in white populations. 169,170,172,175 However, the frequency of the minor T allele of this variant is much lower in many other population groups (www.ensembl.org) and therefore unlikely to be informative within all populations. 185 Hence, investigators should identify appropriate informative genetic markers for other population groups.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

See 1 more Smart Citation

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

Shultz

Schmitz

Benjaminse

et al. 2015

Journal of Athletic Training

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Section: Genetic Risk Factorsmentioning

confidence: 99%

Section: Genetic Risk Factorsmentioning

confidence: 99%

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

Shultz

Schmitz

Benjaminse

et al. 2015

Journal of Athletic Training

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“…Type I collagen (Col I), and its two coding genes COL1A1 and COL1A2, will also be discussed because it forms the major structural component of tendon, even though genetic variation has not yet been associated with tendinopathies or tendon properties. Associations have, however, been observed between genetic variation in COL1A1 and risk of ligament injury [43,44]. This article will review genes and proteins that are known to be related to tendon structure and/or the dynamic nature of tendon homeostasis, and the review will describe how variations within these genes may affect human tendon mechanical properties such as stiffness and elastic modulus.…”

Section: Tendon Propertiesmentioning

confidence: 99%

Genetic Variation, Protein Composition and Potential Influences on Tendon Properties in Humans

Foster¹

2012

TOSMJ

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Sequence variations in genes that code for proteins involved in homeostatic processes within tendons may influence tendon mechanical properties. Since variants of the four genes COL5A1, TNC, MMP3 and GDF5 have been implicated in the aetiopathogenesis of tendinopathies, which is ultimately characterised by abnormal structural and regulatory processes, sequence variations in these four genes may also influence how the tendon functions mechanically, even in the absence of tendinopathy. For example, two reports of association between variation in the COL5A1 gene and measures of flexibility complement reported associations between genotype and incidence of tendinopathy. Non-genetic factors such as age, body mass and physical activity status influence risk of tendon injury and physical performance potential independently from genomics, and also in gene-environment interactions. However, these non-genetic factors are often not considered in genetic association studies, probably due to their retrospective nature. Further research examining COL5A1, TNC, MMP3 and GDF5, as well as other genes that may influence the maintenance of tendon homeostasis such as COL1A1 which regulates the production of collagen type 1, the most abundant structural component of tendon is encouraged. Establishing the genetic basis of tendon properties in asymptomatic populations may advance understanding of some aspects relevant to physical performance and of the aetiology of tendinopathies. To improve understanding, accurate and reproducible assessments of tendon properties are required. However, no valid and reliable assessments of tendon properties, such as those involving in vivo ultrasound imaging techniques, have yet been applied to genetic association studies in humans.

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“…Such rare variants often have a larger effect on risk as well as greater penetrance, making them good targets for prophylactic treatments (Bodmer & Bonilla, 2008). For example, the rare TT genotype (<5% in Caucasian populations) of the functional Sp1-binding site polymorphism (rs1800012; G>T) within intron 1 of the COL1A1 gene is associated with reduced risk of acute soft tissue ruptures (Collins, Posthumus, & Schwellnus, 2009;Khoschnau et al, 2008;Posthumus et al, 2009). Associations of common multifactorial diseases with rare variants are unlikely to be found by either genome-wide association studies or casecontrol association studies such as the current study, and further work would therefore be necessary to test this hypothesis (Bodmer & Bonilla, 2008).…”

Section: Discussionmentioning

confidence: 99%

Variants within theCOMPandTHBS2genes are not associated with Achilles tendinopathy in a case-control study of South African and Australian populations

Saunders

Merwe

Cook

et al. 2013

Journal of Sports Sciences

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Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.

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Type I Collagen α1 Sp1 Polymorphism and the Risk of Cruciate Ligament Ruptures or Shoulder Dislocations

Abstract: The authors found a substantially decreased risk of these injuries associated with collagen type I alpha1 Sp1 polymorphism. The study might encourage other investigators to consider further research in the area of genes and soft tissue injuries.

Cited by 123 publications

References 36 publications

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

Genetic Variation, Protein Composition and Potential Influences on Tendon Properties in Humans

Variants within theCOMPandTHBS2genes are not associated with Achilles tendinopathy in a case-control study of South African and Australian populations

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