Interactions between collagen gene variants and risk of anterior cruciate ligament rupture
O’Connell K., Knight H., Ficek K., Leonska-Duniec A., Maciejewska-Karlowska A., Sawczuk M., Stepien-Slodkowska M., O’Cuinneagain D., van der Merwe W., Posthumus M., Ciezczyk P., Collins M. Eurpoean Journal of Sport Science.
Take Home Message: An individual with a specific genetic variation related to collagen type III may be more likely to have an ACL injury. Additionally a gene-gene interaction may exist between two genetic variants related to collagen that increase the risk of ACL injury in females.
Various types of collagen (for example, types III, V, VI, XII) are present in the anterior cruciate ligament (ACL). We’ve previously seen evidence that genetic variations among genes that produce components of the ACL may increase the risk of ACL tears but very few investigators have looked at the risk of an ACL injury when someone has multiple genetic variations. Four genes of interest may be those that produce types III, V, VI, and XII collagen. Therefore, the authors investigated whether individual gene variants within COL3A1, COL6A1, COL5A1, and COL12A1, as well as the combination of these variants increased the risk of ACL rupture. The authors explored these genetic variants in 2 different populations. The first population consisted of 477 Caucasian South African of which 242 (177 male, 65 female) were surgically diagnosed with an ACL rupture and 235 (145 male, 90 females) self-reported no history of an ACL injury. The second group consisted of 234 Polish participants, where 91 participants (71 male, 20 female) were surgically diagnosed with an ACL rupture and 143 (99 male, 44 female) self-reported no previous ACL injury. The authors matched the injured and uninjured participants in each cohort for weight and height. Additionally, the Polish group was matched for sex. To determine gene-gene interaction researchers used previous genes that were individually associated with ACL injury risk (COL5A1 and COL12A1) and separately analyzed male and female subgroups. The researchers demonstrated an association within the Polish cohort between a COL3A1 variant and ACL rupture, where those carrying that variation were almost 4 times more at risk for an ACL rupture compared with controls. No genetic associations to ACL ruptures were found within the South African cohort. Finally, there was a gene-gene interaction among females in both cohorts. Females carrying a COL5A1 variation and the COL12A1 variation were more likely to have an ACL injury compared with females not carrying these variations. There were no gene-gene interactions within the male sub-group.
This was a novel study that found that there may be a gene-gene interaction that increases a female’s risk to ACL rupture. The interaction is important because if we only looked at one genetic variation it may mask the risk because the true risk required a second variation to be present. This highlights the complexity of using genetic risk factors. If we want to use genetic testing to identify a patient at high risk we may need to look at the whole genetic picture, or as much as possible. Owing to the fact that an ACL injury has many intrinsic and extrinsic factors contributing to the risk, future research should consider further gene-gene interactions as well as the role of an interaction between environment and genetics. Clinically, these findings may help explain why females may be at a greater risk of ACL injury, and medical personnel should be educating females on these risks as well as preventative measures.
Questions for Discussion: Does knowing genetic risk change how you educate athletes on risks and prevention for ACL injuries? Do you think genetic screening could lead to better preventative measures?
Written by: Jane McDevitt, PhD
Reviewed by: Jeff Driban