The Apoptosis Pathway and <i>CASP8</i> Variants Conferring Risk for Acute and Overuse Musculoskeletal Injuries

Seale, Kirsten; Burger, Marilize; Posthumus, Michael; Häger, Charlotte; Stattin, Eva‐Lena; Nilsson, Kjell; Collins, Malcolm; September, Alison V.

doi:10.1002/jor.24504

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…The influence of genes and associated polymorphisms has previously been suggested to play a role for knee injury [96]. Results from different studies are, however, conflicting and there is currently no convincing evidence that specific genotypes will pre-dispose individuals to ACL injury [96][97][98][99][100]. Genetic variations in the form of inherited anatomical or biomechanical alterations may, however, be important for injury risk.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Contra-Lateral Secondary Anterior Cruciate Ligament Injury: A Systematic Review with Meta-Analysis

2021

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Background The risk of sustaining a contra-lateral anterior cruciate ligament (C-ACL) injury after primary unilateral ACL injury is high. C-ACL injury often contributes to a further decline in function and quality of life, including failure to return to sport. There is, however, very limited knowledge about which risk factors that contribute to C-ACL injury. Objective To systematically review instrinsic risk factors for sustaining a C-ACL injury. Methods A systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases (MEDLINE, CINAHL, EMBASE, Sport Discus) were searched from inception to January 2020. Inclusion criteria were prospective or retrospective studies investigating any intrinsic risk factor for future C-ACL injury. Meta-analysis was performed and expressed as odds ratios (OR) if two or more articles assessed the same risk factor. Results 44 moderate-to-high quality studies were eventually included in this review, whereof 35 studies were eligible for meta-analysis, including up to 59 000 individuals. We identified seven factors independently increasing the odds of sustaining a C-ACL injury (in order of highest to lowest OR): (1) returning to a high activity level (OR 3.26, 95% CI 2.10–5.06); (2) Body Mass Index < 25 (OR 2.73, 95% CI 1.73–4.36); (3) age ≤ 18 years (OR 2.42, 95% CI 1.51–3.88); (4) family history of ACL injury (OR 2.07, 95% CI 1.54–2.80); (5) primary ACL reconstruction performed ≤ 3 months post injury (OR 1.65, 95% CI: 1.32–2.06); (6) female sex (OR 1.35, 95% CI 1.14–1.61); and (7) concomitant meniscal injury (OR 1.21, 95% CI 1.03–1.42). The following two factors were associated with decreased odds of a subsequent C-ACL injury: 1) decreased intercondylar notch width/width of the distal femur ratio (OR 0.43, 95% CI 0.25–0.69) and 2) concomitant cartilage injury (OR 0.83, 95% CI 0.69–1.00). There were no associations between the odds of sustaining a C-ACL injury and smoking status, pre-injury activity level, playing soccer compared to other sports or timing of return to sport. No studies of neuromuscular function in relation to risk of C-ACL injury were eligible for meta-analysis according to our criteria. Conclusion This review provides evidence that demographic factors such as female sex, young age (≤ 18 years) and family history of ACL injury, as well as early reconstruction and returning to a high activity level increase the risk of C-ACL injury. Given the lack of studies related to neuromuscular factors that may be modifiable by training, future studies are warranted that investigate the possible role of factors such as dynamic knee stability and alignment, muscle activation and/or strength and proprioception as well as sport-specific training prior to return-to-sport for C-ACL injuries. PROSPERO: CRD42020140129.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Contra-Lateral Secondary Anterior Cruciate Ligament Injury: A Systematic Review with Meta-Analysis

2021

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“…The limited evidence was found for the lack of association between CASP8 (rs3834129 ins/Del, rs1045485, rs13113) (Rahim et al, 2017;Seale et al, 2020), B-fibrinogenrs (rs1800789, rs1800791) (Zhao et al, 2020), PTGER4 (rs4495224) (Rahim et al, 2017) and TIMP2 (rs4789932 ) (Lulinska-Kuklik et al, 2019d;Rahim et al, 2019) variants and ACL injury. In addition, there was insufficient evidence to link Adiponectin rs1501299 (OR = 1.91) and B-fibrinogenrs (1800787, rs1800788, rs1800790, rs2227389) (Zhao et al, 2020) to the ACL injury.…”

Section: Influence Of Genetic Factors On the Aclrmentioning

confidence: 99%

Genetic Determinants of the Anterior Cruciate Ligament Rupture in Sport: An Up-to-Date Systematic Review

Sun¹,

Humińska-Lisowska²,

Michałowska–Sawczyn³

et al. 2023

Journal of Human Kinetics

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Anterior cruciate ligament injuries (ACLIs) are one of the most common knee injuries in sports. Although numerous factors have been related to the risk of ACLIs, it is still unclear why some individuals are more susceptible than others due to the intricate etiology of ACLIs. Several genetic factors have been identified as contributing to ACLIs. This systematic review summarizes the current evidence regarding the genetic causes of ACLIs based on the available literature. Five electronic databases were searched from 2017 to 2022. All titles, abstracts, and full texts were reviewed in detail to determine the inclusions and exclusions. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. The studies' characteristics and results are presented in both narrative and tabular formats. A total of 24 studies examined 31 genes and 62 variants associated with ACLIs in the global population. Ten studies investigated seven collagens and ten SNPs for the ACL injury. The majority of studies found no significant difference in the association of the COL1A1 rs1800012, COL5A1 rs12722, VEGFA rs1570360, IL6R rs2228145, IL6 rs1800795, IL1B rs16944 and rs1143627, however, contrary results were found when nationality and gender were considered together. Conflicting evidence was found for polymorphisms rs2010963, rs699947 of the VEGFA gene in different studies. Due to a lack of data, it was impossible to determine the relationship between the anterior cruciate ligament rupture (ACLR) and the other polymorphisms. More research is required to establish a clear relationship between the ACLR and genetic variants, particularly when gender and nationality are taken into account separately.

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“…Both Rahim and Seale have reported associations between caspase functional gene variants and ACL ruptures [ 174 , 175 ].…”

Section: Ligament: Structure Function and Genetic Researchmentioning

confidence: 99%

Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review

Ribbans

September

Collins

2022

Life

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A significant proportion of patients requiring musculoskeletal management present with tendon and ligament pathology. Our understanding of the intrinsic and extrinsic mechanisms that lead to such disabilities is increasing. However, the complexity underpinning these interactive multifactorial elements is still not fully characterised. Evidence highlighting the genetic components, either reducing or increasing susceptibility to injury, is increasing. This review examines the present understanding of the role genetic variations contribute to tendon and ligament injury risk. It examines the different elements of tendon and ligament structure and considers our knowledge of genetic influence on form, function, ability to withstand load, and undertake repair or regeneration. The role of epigenetic factors in modifying gene expression in these structures is also explored. It considers the challenges to interpreting present knowledge, the requirements, and likely pathways for future research, and whether such information has reached the point of clinical utility.

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The Apoptosis Pathway and CASP8 Variants Conferring Risk for Acute and Overuse Musculoskeletal Injuries

Cited by 6 publications

References 48 publications

Risk Factors for Contra-Lateral Secondary Anterior Cruciate Ligament Injury: A Systematic Review with Meta-Analysis

Risk Factors for Contra-Lateral Secondary Anterior Cruciate Ligament Injury: A Systematic Review with Meta-Analysis

Genetic Determinants of the Anterior Cruciate Ligament Rupture in Sport: An Up-to-Date Systematic Review

Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review

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