A pinboard by
Samantha Beckley

PhD Student, University of Cape Town


Can specific genetic variants affect one's knee laxity and in turn affect risk of ACL injury?

The aim of my research is to investigate the association between genetic differences within genes encoding collagen as well as other extracellular matrix proteins and knee joint laxity. Collagen is the primary unit of musculoskeletal soft tissue structures, such as tendons and ligaments. In the case of my study, I will be focusing on one particular ligament, the anterior cruciate ligament (ACL). The ACL is a very important structure within the knee joint as is inhibits excessive forward and twisting movement of the tibia. Injury to the ACL is extremely costly and often has lifelong effects, such as increasing one's likelihood of developing early onset osteoarthritis.

In previous studies, measurements of knee laxity have been associated with the risk of sustaining an ACL rupture. Furthermore, research has also demonstrated an association between collagen gene variants and risk of ACL rupture. Some of these variants have also shown an association with range of motion and knee laxity measurements. More recent studies have implicated variants within other matrix coding genes to be associated with risk of ACL rupture. More research is needed in this field in order to gain a better understanding of the role of these genetic variants in knee joint laxity, and in turn, will improve our understanding of the etiology of ACL ruptures.

We will be recruiting 200 participants, 100 participants will have no history of ACL tears or ruptures and the other 100 participants will have previously undergone ACL surgery on one leg. A small blood sample will be taken from each participant. This sample will be used for genotyping in our laboratory. The participants will then have a number of knee laxity measurements performed. Using statistical software will determine whether a link exists between knee laxity measurements, genetics as risk of ACL rupture.


Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant.

Abstract: Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury is not yet fully understood. Recently, the gene encoding for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with cruciate ligament ruptures and shoulder dislocations.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.117 Caucasian participants with surgically diagnosed ACL ruptures, and 130 Caucasian physically active controls without any history of previous ligament or tendon injuries were recruited for this case-control genetic association study. All 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%).The TT genotype of the COL1A1 Sp1 binding site polymorphism was significantly under-represented in South African participants with ACL ruptures. We propose that this sequence variant be the first specific genetic element to be included in multifactorial models developed to understand the aetiology and risk factors for ACL rupture.

Pub.: 06 Feb '09, Pinned: 27 Jul '17

Rotational laxity greater in patients with contralateral anterior cruciate ligament injury than healthy volunteers.

Abstract: Rotational stability of the knee has been traditionally difficult to quantify, limiting the ability of the orthopedic community to determine the potential role of rotational laxity in the etiology of anterior cruciate ligament (ACL) injuries. The purposes of this multicenter cohort study were to evaluate the reliability of a robotic axial rotation measurement system, determine whether the uninjured knees of patients that had previous contralateral ACL reconstruction demonstrated different rotational biomechanical characteristics than a group of healthy volunteers, and determine whether knee rotational biomechanical characteristics differ between male and female non-injured limbs in groups of both healthy volunteers and patients with a previous contralateral ACL injury. Fourteen healthy volunteers and 79 patients with previous unilateral ACL injury participated in this study. Patients were tested using a computerized tibial axial rotation system. Only the normal (non-operated) knee data were used for analysis. In order to assess the reliability of the robotic measurement system, 10 healthy volunteers were tested daily over four consecutive days by four different examiners. Rotational laxity and compliance measures demonstrated excellent reliability (ICC = 0.97). Patients with a contralateral ACL injury demonstrated significantly increased tibial internal rotation (20.6° vs. 11.4°, P < 0.001) and reduced external rotation (16.7° vs. 26.6°, P < 0.001) compared to healthy volunteers. Females demonstrated significantly increased internal and external rotation, as well as significantly increased rotational compliance compared with males (P < 0.05). Computer-assisted measurement techniques may offer clinicians an accurate, reliable, non-invasive method to select the most appropriate preventative or surgical interventions for patients with increased knee rotational laxity.

Pub.: 19 Dec '09, Pinned: 27 Jul '17

The COL5A1 gene is associated with increased risk of anterior cruciate ligament ruptures in female participants.

Abstract: Anterior cruciate ligament ruptures, especially to young female athletes, are a cause of major concern in the sports medicine fraternity. The major structural constituents of ligaments are collagens, specifically types I and V. Recently, the gene that encodes for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with an increased risk of cruciate ligament ruptures. The COL5A1 gene, which encodes for the alpha1 chain of type V collagen, has been shown to be associated with Achilles tendon injuries.The study was conducted to determine (1) if 2 sequence variants (BstUI and DpnII restriction fragment length polymorphisms [RFLPs]) within the COL5A1 gene are associated with an increased risk of anterior cruciate ligament ruptures, and (2) if there were any gender-specific positive associations between the 2 COL5A1 sequence variants and risk of anterior cruciate ligament ruptures.Case control study; Level of evidence, 3.A total of 129 white participants (38 women) with surgically diagnosed anterior cruciate ligament ruptures and 216 physically active control participants (84 women) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the COL5A1 BstUI and DpnII RFLPs.There was a significant difference in the BstUI RFLP genotype frequency between the anterior cruciate ligament rupture and physically active control groups among the female participants, but not the male participants. The CC genotype in the female participants was significantly underrepresented in the anterior cruciate ligament rupture group compared with the controls (27.4% vs 5.6%; odds ratio = 6.6; 95% confidence interval, 1.5-29.7; P = .006). There were no differences in the DpnII RFLP genotype distributions between the anterior cruciate ligament rupture and physically active control groups.The CC genotype of the COL5A1 BstUI RFLP was underrepresented in female participants with anterior cruciate ligament ruptures.This is the first study to show that there is a specific genetic risk factor associated with risk of anterior cruciate ligament ruptures in female athletes.

Pub.: 06 Aug '09, Pinned: 27 Jul '17

Collagen gene variants previously associated with anterior cruciate ligament injury risk are also associated with joint laxity.

Abstract: Genetic association studies demonstrate a relationship between several collagen gene variants and anterior cruciate ligament (ACL) injury, yet the mechanism of these relationships is still unclear. Joint laxity is a heritable trait; increased magnitudes of anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) have been consistently associated with a greater risk of ACL injury. Joint laxity may constitute an important intermediate phenotype for the genetic association with ACL injury that can be measured clinically.To determine if genetic variants within the COL1A1, COL5A1, and COL12A1 genes, previously associated with ACL injury, were also associated with greater magnitudes of AKL, GR, and GJL.Descriptive laboratory study.Blood samples and measures of AKL, GR, and GJL were obtained from 124 (50 male, 74 female) healthy, recreationally active subjects. Genomic DNA was extracted from the blood samples and genotyped for single-nucleotide polymorphisms previously examined relative to ACL injury. Univariate analyses of variance compared the magnitude of each laxity variable across the 3 genotypes for each single-nucleotide polymorphism in both sex-combined and sex-specific models.Specific genotypes were associated with greater GR in all subjects. Some genotypes were associated with greater magnitudes of GR, AKL, and GJL in females only.Gene variants previously associated with ACL injury risk were in large part also associated with joint laxity. Sex-specific genetic associations with joint laxity were consistent with those previously reported for ACL injury.These data provide insight into potential pathways through which genotypic variants in collagen genes have the potential to alter ligament structure and behavior and, thus, ACL injury risk.

Pub.: 28 Sep '12, Pinned: 27 Jul '17