Interactions between
collagen gene variants and risk of anterior cruciate ligament rupture

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.

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.

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

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?

by: Jane McDevitt, PhD
by: Jeff Driban


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, Cieszczyk P, & Collins M (2014). Interactions between collagen gene variants and risk of anterior cruciate ligament rupture. European Journal of Sport Science, 1-10 PMID: 25073002