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The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury.
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MedLine Citation:
PMID:  24744467     Owner:  NLM     Status:  PubMed-not-MEDLINE    
OBJECTIVES: The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study.
METHODS: A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method.
RESULTS: Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher's exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test).
CONCLUSIONS: The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.
M Stępien-Słodkowska; K Ficek; J Eider; A Leońska-Duniec; A Maciejewska-Karłowska; M Sawczuk; A Zarębska; Z Jastrzębski; A Grenda; K Kotarska; P Cięszczyk
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Publication Detail:
Type:  Journal Article     Date:  2013-01-21
Journal Detail:
Title:  Biology of sport / Institute of Sport     Volume:  30     ISSN:  0860-021X     ISO Abbreviation:  Biol Sport     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2014-04-18     Completed Date:  2014-04-18     Revised Date:  2014-04-21    
Medline Journal Info:
Nlm Unique ID:  8700872     Medline TA:  Biol Sport     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  57-60     Citation Subset:  -    
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Journal Information
Journal ID (nlm-ta): Biol Sport
Journal ID (iso-abbrev): Biol Sport
Journal ID (publisher-id): JBS
ISSN: 0860-021X
ISSN: 2083-1862
Publisher: Institute of Sport in Warsaw
Article Information
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Copyright © Biology of Sport 2013
Accepted Day: 07 Month: 11 Year: 2012
Electronic publication date: Day: 21 Month: 1 Year: 2013
Print publication date: Month: 3 Year: 2013
Volume: 30 Issue: 1
First Page: 57 Last Page: 60
PubMed Id: 24744467
ID: 3944561
Publisher Id: 1029823
DOI: 10.5604/20831862.1029823

M. Stępien-Słodkowska1
K. Ficek12
J. Eider1
A. Leońska-Duniec13
A. Maciejewska-Karłowska15
M. Sawczuk15
A. Zarębska3
Z. Jastrzębski3
A. Grenda4
K. Kotarska1
P. Cięszczyk3
1University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland
2Galen Medical Center, Bieruń, Poland
3Academy of Physical Education and Sport, Department of Sport Education, Gdańsk, Poland
4West Pomeranian Technological University, Department of Physical Education and Sport, Szczecin, Poland
5University of Szczecin, Department of Genetics, Poland
Correspondence: Reprint request to: Paweł Cięszczyk, Academy of Physical Education and Sport, Department of Sport Education, ul. Kazimierza Górskiego 1, 80-336 Gdańsk, Poland. Fax +48 58 55 47 324. E-mail:


The popularity of alpine skiing has significantly increased over the last few decades. Current sports technology allows for extreme racing manoeuvres at high speed. Modern slope designs often demand substantial risk taking and advanced skills. Consequently, alpine sports range amongst the most injurious tourist activities [12].

Skiing injuries account for a significant proportion of all sport-related injuries and among these lower extremity injuries account for the vast majority. In an analysis of the distribution of injuries during alpine skiing accidents, lower extremity injuries (39%) pre-dominated followed by upper extremity injuries (34%) [10]. Polish skiers also experience worrying injuries of lower extremities (65%), mainly sprains in the knee joints [3]. The knee is the most commonly injured body part, and is also predominant among severe injuries [7]. Ninety percent of knee ligament injuries involve the anterior cruciate ligament (ACL) or medial collateral ligament (MCL) [21]. Alpine skiing is a high-risk sport for injuries to the ACL [6, 11] because while descending a hill, a skier must resist large centrifugal forces at a high velocity, while the knees are positioned in postures that place the ACL at risk of injury [16]. The important roles of the anterior cruciate ligament regarding knee stability, physiological kinematics, and proprioception are unquestioned [18]. The ACL is a stable static structure with mechanoreceptors distributed across its surface and can regulate dynamic stability by means of the neuromuscular reflex. ACL deficiency causes deficits in proprioception and balance, a decrease in muscular strength and functional performance, and biomechanical modifications of the injured lower limb [26].

The dense fibrous connective tissue of the ACL is composed of a large amount of collagen fibres arranged in a hierarchal pattern, giving it high tensile strength [28]. Ligament fibroblasts produce a number of extracellular matrix (ECM) components, including collagen types I and III, decorin and fibromodulin. Type I collagen comprises 95% of the total ligamentous collagen, but smaller amounts of types III, V, XII, and XIV collagen are also present. The fibrillar type III collagen forms heterogeneous collagen fibrils with type I collagen, but may inhibit collagen fibril diameter growth. Surrounding the collagen fibrils is an organic substance consisting of proteoglycans and glycosaminoglycans. Two abundant proteoglycans within the ligament include decorin and fibromodulin. These proteoglycans bind type I collagen and regulate collagen fibrillogenesis [2].

Collagen, specifically collagen type I, is the most abundant protein in tendon tissue, forming 60–80% of its dry weight. Collagen type III is found in significantly lower abundance than collagen type I, but increased expression is an indicator of tendon injury. Collagen turnover, an important component of a healthy ECM, is regulated by a group of enzymes called matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) [27].

Collagen type I is a heterotrimer consisting of two alpha 1 chains and one alpha 2 chain. It is initially synthesized as a pro-alpha chain with a propeptide at each end (N-propeptide and C-propeptide) [1]. The proteins are encoded by the COL1A1 and COL1A2 genes [5]. The gene that encodes for the alpha 1 chain of type I collagen is located on chromosome 17q21 [30]. Mutations within this gene have been shown to cause connective tissue disorders such as osteogenesis imperfecta or Ehlers-Danlos syndrome [5], systemic diseases with scleral thinning, and myopia [30].

Single nucleotide polymorphisms (SNPs) in the collagen type I (COL1A1) gene have been shown to be associated with several complex connective tissue disorders. The G to T substitution in an intronic Sp1 binding site (rs1800012), resulting in increased affinity for the transcription factor Sp1, and increased gene expression, has been one of the most extensively investigated polymorphisms within this gene [5]. COL1A1 has also been shown to be associated with an increased risk of shoulder dislocations [19], Achilles tendon ruptures and Achilles tendinopathy [5]. Studies have also shown an association of another polymorphism with the risk of ACL rupture [20]. Posthumus et al. found that a rare TT genotype of the Sp1 polymorphism was significantly underrepresented among participants with ACL ruptures [19]. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012). It was theorized that a variant allele T of the Sp1 binding site polymorphism enhances the binding of the transcription factor Sp1, thereby increasing COL1A1 expression and the production rate of alpha-1 chains, resulting in alpha-1 homotrimer production.

The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study.

Study subjects

A total of 138 male recreational skiers (27±2) with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers (26±3) with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury.

Ethics Committee

The Pomeranian Medical University Ethics Committee approved the study and written informed consent was obtained from each participant.

Determination of COL1A1 genotypes

Genomic DNA was extracted from the oral epithelial cells using Gen-Elute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany) according to the manufacturer's protocol. Allelic discrimination of the COL1A1 +1245G/T (rs1800012) polymorphic site was performed using TaqMan Pre-Designed SNP Genotyping Assays (Applied Biosystems, USA), including primers and fluorescently labelled (FAM and VIC) MGB probes for the detection of alleles. All samples were genotyped on a Rotor-Gene real-time polymerase chain reaction (PCR) instrument (Corbett, Australia). Thermal cycler conditions were as follows: an initial step at 95°C for 5 min, followed by 45 cycles of denaturation at 94°C for 15 s and anneal/extend at 60°C for 1 min [13].

Statistical analysis

Any differences in genotype and allele frequency were analysed using χ2 tests (or Fisher's exact test). Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated. All calculations were performed using STATISTICA data analysis software system, version 10 (StatSoft, Inc., 2011;, except Hardy-Weinberg equilibrium, which was tested with the programming language and environment R ( P values <0.05 were considered statistically significant.


The distributions of the COL1A1 genotypes and alleles are given in Table 1. We did not observe a statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test). The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T. Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium: p = 0.2469 and p = 0.33, respectively. Owing to the small number of observations, we used the “collapsing cells method” to determine the statistical significance of genotype distribution (i.e. we made the calculation GG vs. GT and TT). We found a significant difference in the genotype distribution between injured skiers and controls (p = 0.045, Fisher's exact test).


The anterior cruciate ligament is necessary for normal knee stability and movement. Unfortunately, the ACL is also the most frequently injured ligament of the knee, with severe disruptions requiring surgical intervention [9]. ACL rupture affects the loading pattern at the joint interfaces and the stability of the knee, which leads to abnormal loading of articular cartilage during functional activities, and ultimately to articular cartilage degeneration and progressive osteoarthritis of the knee [26]. It is estimated that 27 million adults in the United States have clinical osteoarthritis, with knee osteoarthritis being the most prevalent form, affecting 28% of adults over age 45 and 37% of adults over age 60. The most significant cause of osteoarthritis in young adults is joint trauma including tears of the menisci or ligaments [29]. The incidence of knee osteoarthritis in patients with untreated ACL deficiency 11 years after ACL rupture is as high as 44% [26].

A skier's risk of injury depends on a considerable number of different factors [14]. Skiing injuries may result from an individual overestimating his or her abilities or from fatigue. [10]. Snow, slope and weather conditions, as well as altitude and low temperatures, are thought to influence the prevalence of knee injuries [22]. Analysis of menstrual history data revealed that recreational skiers in the preovulatory phase were significantly more likely to sustain an ACL injury than were skiers in the postovulatory phase [23]. Although intrinsic and extrinsic factors for ACL ruptures have been identified, the exact aetiology of this injury is not yet fully understood [17].

Some studies have also suggested a genetic predisposition to Achilles tendon ruptures and chronic Achilles tendinopathy, as well as to tears of the ACL [25]. It was previ¬ously shown that individuals who had a family history of ACL rupture exhibited 2-fold higher risk for ACL rupture [8]. In the present study, the aim was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in male skiers in a case-control study. There was a significant difference in the genotype distribution between skiers and controls, but there was no statistical difference in allele distribution. The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.

Three studies have suggested that the rare TT genotype of functional Sp1 binding site polymorphism within intron 1 of COL1A1 is associated with infrequency of cruciate ligament ruptures (CL), shoulder dislocation (SD) and Achilles tendon ruptures [4]. Collins et al. found that similar genotype distributions were reported for the control and injury groups in all three studies [4]. The TT genotype, when compared to the control group (4.1%, n = 24 of 581), was significantly under-represented in the (1) CL (0.3%, n = 1 of 350, OR = 15.0, P = 0.0002), (2) CL and SD (0.4% TT genotype, n = 2 of 476, OR = 10.2, P < 0.0001), and (3) CL, SD and Achilles tendon ruptures (0.4% TT genotype, n = 2 of 517, OR = 11.1, P < 0.0001) groups. This combined analysis indicates that the TT genotype appears to be protected against acute soft tissue ruptures and should be incorporated into multi-factorial models determining risk for acute soft tissue ruptures [4].

Posthumus et al. sought to determine whether the functional Sp1 binding site polymorphism within intron 1 of the COL1A1 gene is associated specifically with ACL ruptures in an independent population [19]. All Caucasian participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012). The rare TT genotype was significantly (p = 0.031, OR = 0.08, 95% CI <0.01 to 1.46) under-represented in the ACL group (0 out of 117, 0%), compared with the controls (6 out of 130, 4.6%) [19].

Similar results were obtained in studies conducted among patients with cruciate ligament rupture and shoulder dislocation. Compared with the homozygous SS category, the heterozygous participants displayed a similar risk (OR, 1.06; 95% CI, 0.76-1.49), whereas the ss genotype was underrepresented in the injured population compared with the controls (OR, 0.15; 95% CI, 0.03-0.68). This latter estimate was similar for both cruciate ligament ruptures and shoulder dislocations, and was furthermore not modified by general joint laxity. Varying levels of risk of these injuries were found in association with collagen type I alpha 1 Sp1 polymorphisms [15].

The role of genetics in sport research increases with every passing year. Knowledge of the role of individual genes in the processes occurring in the human body can also be used in sport rehabilitation and injury prevention. Precise determination of genotypes at risk for acute or chronic diseases related to sport will probably allow changes in individual training plans to greatly minimize the risk of injury [24].


In conclusion, in our study the risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.

1. Ben Amor M,Glorieux F.H,Rauch F. Genotype-phenotype correlations in autosomal dominant osteogenesis imperfectaJ. Osteoporos.Year: 201110.4061/2011/540178
2. Chamberlain C.S,Crowley E.M,Kobayashi H,Eliceiri K.W,Vanderby R. Quantification of collagen organization and extracellular matrix factors within the healing ligamentMicrosc. Microanal.Year: 20111777978721910939
3. Chojnacki K. The risk of ski accidents on the area of TOPR in the period between 2001 and 2005Med. SportowaYear: 2007164649 (in Polish).
4. Collins M,Posthumus M,Schwellnus M. The COL1A1 gene and acute soft tissue rupturesBr. J. Sports Med.Year: 2010441063106419193665
5. Collins M,Raleigh S.M. Genetic risk factors for musculoskeletal soft tissue injuriesMed. Sport Sci.Year: 20095413614919696512
6. Dragoo J.L,Braun H.J,Durham J.L,Chen M.R,Harris A.H. Incidence and risk factors for injuries to the anterior cruciate ligament in national collegiate athletic association football: data from the 2004-2005 through 2008-2009 national collegiate athletic association injury surveillance systemAm. J. Sports Med.Year: 20124099099522491794
7. Florenes T.W,Heir S,Nordsletten L,Bahr R. Injuries among World Cup freestyle skiersBr. J. Sports Med.Year: 20104480380820820059
8. Flynn R.K,Pedersen C.L,Birmingham T.B,Kirkley A,Jackowski D,Fowler P.J. The familial predisposition toward tearing the anterior cruciate ligament: a case control studyAm. J. Sports Med.Year: 200533232815610995
9. Freeman J.W,Woods M.D,Cromer D.A,Ekwueme E.C,Andric T,Atiemo E.A,Bijoux C.H,Laurencin C.T. Evaluation of a hydrogel-fiber composite for ACL tissue engineeringJ. Biomech.Year: 2011Day: 24 4469469921111422
10. Greier K. Skiing injuries in school sport and possibilities to prevent themSportverletz SportschadenYear: 20112521622122161263
11. Hansom D,Sutherland A. Injury prevention strategies in skiers and snowboardersCurr. Sports Med. Rep.Year: 2010916917520463501
12. Hasler R.M,Schmucker U,Evangelopoulos D.S,Hirschberg R.E,Zimmermann H,Exadaktylos K. Improving prehospital trauma management for skiers and snowboarders need for on-slope triage?J. Trauma Manag. OutcomesYear: 20115521521524
13. Higuchi R,Rockler C,Dollinger G,Watson R. Kinetic PCR analysis: real-time monitoring of DNA amplification reactionsBiotechnologyYear: 199311102610307764001
14. Hildebrandt C,Mildner E,Hotter B,Kirschner W,Höbenreich C,Raschner C. Accident prevention on ski slopes - Perceptions of safety and knowledge of existing rulesAccid Anal. Prev.Year: 2011431421142621545875
15. Khoschnau S,Melhus H,Jacobson A,Rahme H,Bengtsson H,Ribom E,Grundberg E,Mallmin H,Michaëlsson K. Type I collagen alpha1 Sp1 polymorphism and the risk of cruciate ligament ruptures or shoulder dislocationsAm. J. Sports Med.Year: 2008362432243618669982
16. Kokmeyer D,Wahoff M,Mymern M. Suggestions from the field for return-to-sport rehabilitation following anterior cruciate ligament reconstruction: alpine skiingJ. Orthop. Sports Phys. Ther.Year: 20124231332522467124
17. Malila S,Yuktanandana P,Saowaprut S,Jiamjarasrangsi W,Honsawek S. Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament rupturesGenet. Mol. Res.Year: 2011104158416522057989
18. Nowakowski A.M,Stangel M,Grupp T.M,Valderrabano V. Investigating the primary stability of the transversal support tibial plateau concept to retain both cruciate ligaments during total knee arthroplastyJ. Appl. Biomater. Biomech.Year: 2012 Epub ahead of print.
19. Posthumus M,September A.V,Keegan M,O'Cuinneagain D,Van der Merwe W,Schwellnus M.P,Collins M. Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant.2009Br. J. Sports Med.Year: 20094335235619193663
20. Posthumus M,September A.V,O'Cuinneagain D,van der Merwe W,Schwellnus M.P,Collins M. The COL5A1 gene is associated with increased risk of anterior cruciate ligament ruptures in female participantsAm. J. Sports Med.Year: 2009372234224019654427
21. Rathbone S,Maffulli N,Cartmell S.H. Most British surgeons would consider using a tissue-engineered anterior cruciate ligament: A questionnaire studyStem. Cells Int.Year: 20122012303724 Epub 2012 Feb 26. 22567023
22. Ruedl G,Fink C,Schranz A,Sommersacher R,Nachbauer W,Burtscher M. Impact of environmental factors on knee injuries in male and female recreational skiersScand. J. Med. Sci. SportsYear: 20122218518921477163
23. Ruedl G,Ploner P,Linortner I,Schranz A,Fink C,Sommersacher R,Pocecco E,Nachbauer W,Burtscher M. Are oral contraceptive use and menstrual cycle phase related to anterior cruciate ligament injury risk in female recreational skiers?Knee Surg. Sports Traumatol. Arthrosc.Year: 2009171065106919333573
24. Sawczuk M,Maciejewska A,Cięszczyk P,Eider J. The role of genetic research in sportSci. SportsYear: 201126251258
25. September A.V,Schwellnus M.P,Collins M. Tendon and ligament injuries: the genetic componentBr. J. Sports Med.Year: 20074124124617261551
26. Shi D,Wang Y,Ai Z. Effect of anterior cruciate ligament reconstruction on biomechanical features of knee in level walking: a meta-analysisChin. Med. J.Year: 20101233137314221162970
27. Sullivan B.E,Carroll C.C,Jemiolo B,Trappe S.W,Magnusson S.P,Døssing S,Kjaer M,Trappe T.A. Effect of acute resistance exercise and sex on human patellar tendon structural and regulatory mRNA expressionJ. Appl. Physiol.Year: 200910646847519023016
28. Tovar N,Bourke S,Jaffe M,Murthy S.N,Kohn J,Gatt C,Dunn M.G. A comparison of degradable synthetic polymer fibers for anterior cruciate ligament reconstructionJ. Biomed. Mater. Res. AYear: 20109373874719623532
29. Trent M,Stylianou A. Simulation of anterior cruciate ligament deficiency in a musculoskeletal model with anatomical kneesOpen Biomed. Eng. J.Year: 20126233222470411
30. Zhang D,Shi Y,Gong B,He F,Lu F,Lin H,Wu Z,Cheng J,Chen B,Liao S,Ma S,Hu J,Yang Z. An association study of the COL1A1 gene and high myopia in a Han Chinese populationMol. Vis.Year: 2011173379338322219633

[TableWrap ID: T0001] TABLE 1 


Group n COL1A1 genotype P* COL1A1 allele P
Injured ACL skiers 138 90
0.046 226
Control 183 139

*Note: GG vs. GT + TT. Data is given as n-values with percentages in parentheses.

Article Categories:
  • Original Paper

Keywords: anterior cruciate ligament (ACL) rupture, COL1A1 gene, collagen, polymorphism, skiers.

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