Is There a Genetic Predisposition to Anterior Cruciate Ligament Tear? A Systematic Review

John, Rakesh; Dhillon, Mandeep Singh; Sharma, Sudhaa; Prabhakar, Sharad; Bhandari, Mohit

doi:10.1177/0363546515624467

Cited by 45 publications

(56 citation statements)

References 28 publications

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“…Nonetheless, studies available are not representative of the general population, limiting the extrapolation of results to general population 30. They concluded that larger, multicentric studies with different ethnic population should be conducted to better understand the role of genetic aetiology in ACL tears.…”

Section: Introduction and Basic Sciencementioning

confidence: 99%

Genetic and molecular factors and anterior cruciate ligament injuries: current concepts

2017

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Section: Introduction and Basic Sciencementioning

confidence: 99%

Genetic and molecular factors and anterior cruciate ligament injuries: current concepts

2017

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“…A best-evidence synthesis provides stronger evidence and takes a different approach to presenting the results than does a simple narrative summary. Consequently, the results and conclusions of the current analysis concerning the associations between genetic variants and ACL injury differ from and have greater methodological power than those of John et al [24]. Second, this review included two additional studies [30, 40].…”

Section: Discussionmentioning

confidence: 95%

“…John et al [24] recently published a systematic review on a topic similar to ours, albeit with some notable methodological differences between the two reviews. In an attempt to conduct more sensitive research, we searched more databases.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review

et al. 2017

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BackgroundStudies have shown a familial predisposition for anterior cruciate ligament (ACL) rupture and have been followed by genetic-association studies on polymorphisms in candidate genes in recent years. To date, no systematic review with a best-evidence synthesis has evaluated the influence of genetics on this devastating knee injury.ObjectiveOur objective was to evaluate the association between genetic variants and ACL rupture.MethodsWe performed an extensive search in Embase, MEDLINE, Web of Science, Scopus, PubMed Publisher, Cochrane Register of Clinical Trials, and Google scholar up to 24 August 2015. Studies were eligible if they met the following inclusion criteria: (1) design was a case–control study, retrospective or prospective follow-up study, or a randomized controlled trial (RCT); (2) the study examined the association between a genetic variant and ACL rupture in both an ACL and a control group. We determined the risk of bias for all included studies.ResultsWe included a total of 16 studies (eight at high risk of bias and eight with an unclear risk) that examined 33 different DNA variants. Conflicting evidence was found for the COL1A1 rs1800012 and COL3A1 rs1800255 variants, whereas limited evidence was found for no association of the COL5A1 rs12722 and rs13946 and COL12A1 rs970547 variants (all encoding collagen). Evidence was insufficient to draw conclusions as to whether any other genetic variant identified in this review had any association with ACL rupture.ConclusionsMore research is needed to support a clear association between ACL rupture and genetic variants. Genome-wide studies are recommended for exploring more potential genetic variants. Moreover, large prospective studies are needed to draw robust conclusions.

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“…Modifiable risk factors are typically extrinsic factors such as footwear (Dowling, Corazza, Chaudhari, & Andriacchi, ) and playing surfaces (Orchard, Chivers, Aldous, Bennell, & Seward, ) and are more obvious and easily addressed than nonmodifiable risk factors. Nonmodifiable risk factors, which are mostly intrinsic and may put certain individuals at heightened risk of injury, include female gender (Hewett, Myer, & Ford, ; Myer, Ford, Paterno, Nick, & Hewett, ), genetic factors (John, Dhillon, Sharma, Prabhakar, & Bhandari, ; Smith et al, ), hormonal factors (Zazulak, Paterno, Myer, Romani, & Hewett, ), static lower limb alignment (Loudon, Jenkins, & Loudon, ; Nguyen, Shultz, & Schmitz, ), and narrow intercondylar notch size (Harner, Paulos, Greenwald, Rosenberg, & Cooley, ; Shelbourne, Davis, & Klootwyk, ). Knowledge of nonmodifiable risk factors is important as it enables the identification of those individuals most vulnerable to injury and to whom prevention training programmes should be directed.…”

Section: Introductionmentioning

confidence: 99%

Generalized joint hypermobility in siblings with anterior cruciate ligament injuries and matched unrelated healthy siblings

Keays

Newcombe

Keays

2020

Physiotherapy Res Intl

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Background and Purpose Anterior cruciate ligament (ACL) ruptures are common knee injuries, and siblings of individuals with an ACL injury may be at higher risk of ACL injury. Generalized hypermobility may be a familial factor predisposing siblings to ACL injury and may also relate to faulty lower limb alignment. There is a need to determine whether the interaction between hypermobility, family history, and faulty alignment makes siblings with hypermobility at higher risk for ACL injury so that appropriate preventative measures can be taken. This study therefore aimed to (a) compare the prevalence of generalized hypermobility and faulty limb alignment in siblings with and without injury and (b) assess the relationship between generalized hypermobility and lower limb alignment. Methods In this case‐controlled study, 24 siblings with ACL injuries from 10 families were matched with 24 healthy uninjured siblings from 10 unrelated families. Generalized hypermobility was assessed using Beighton's criteria. Chi‐square analyses compared generalized hypermobility and lower limb alignment between siblings and sibling pairs with and without injuries. Spearman's rho was used to assess correlations between generalized hypermobility and lower limb alignment. Results There were significant differences between the number of injured and uninjured siblings demonstrating generalized hypermobility when tallied individually (p = .003) and in same‐family sibling pairs (p = .019). Significant (or close) differences were found between siblings for knee hyperextension (p < .001), knee valgus (p = .01), and foot pronation (p = .002) and for sibling pairs sharing knee hyperextension (p < .001), knee valgus (p = .06), and foot pronation (p = .06). Generalized hypermobility correlated with knee hyperextension (rs = .722; p < .001), knee valgus (rs = .385; p = .007), and foot pronation (rs = .328; p = .023). Conclusions Generalized hypermobility and faulty limb alignment occur significantly more frequently in injured than uninjured families. Screening for both features would assist in identifying at‐risk siblings. Prevention programmes reduce ACL injuries by 50–70% and should target hypermobile siblings of the ACL injured.

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Is There a Genetic Predisposition to Anterior Cruciate Ligament Tear? A Systematic Review

Cited by 45 publications

References 28 publications

Genetic and molecular factors and anterior cruciate ligament injuries: current concepts

Genetic and molecular factors and anterior cruciate ligament injuries: current concepts

Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review

Generalized joint hypermobility in siblings with anterior cruciate ligament injuries and matched unrelated healthy siblings

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