The association of genes involved in
the angiogenesis-associated signalizing pathway with risk of anterior cruciate
ligament rupture

Rahim
M, Gibbon A, Hobbs H, van der Merwe W, Posthumus M, Collins M, & September
AV. Journal of Orthopaedic Research. 2014,
32(12):1612-1618.

Take Home Message:  Specific genotypes that influence new blood
vessel growth are more common among individuals with an anterior cruciate
ligament tear.

The growing trend to investigate an
individual’s genetic coding to determine if they are more likely to sustain an
injury can help us identify individuals at risk for injury and understand why
people may be susceptible to injury. Genetic variations that influence the
composition of an anterior cruciate ligament (ACL) may increase the risk of ACL
ruptures (see related posts below).  Genes
that are related to new blood vessel formation (angiogenesis) may influence the
composition of ACLs but no one has examined if genetic variations in these
genes are related to ACL tears.  The
authors of this case-control study aimed to identify if
individuals who had suffered an ACL injury had genetic coding differences from
physically active controls.  Seven
variations (single nucleotide polymorphisms [SNPs]) were analyzed within 4
genes related to new blood vessel formation in 454 participants (227 ACL
injured and 227 matched controls).  ACL
injured participants were more likely to have a variation in the gene for vascular endothelial growth factor A
(VEGFA) than healthy controls (51% versus 42%, respectively).  The authors also completed a sub-analysis of
genetic differences among 126 participants with a noncontact ACL injury.  They found that 1 VEGFA variation was more
common among individuals with a noncontact ACL injury than those in the control
group.  However, another variation within
the same gene was less common among individuals with a noncontact ACL injury.

Genetic
testing may allow clinicians to determine if an individual may be predisposed
to an ACL injury; however, this analysis only makes introductory associations
and needs to be further explored to determine if these genetic variations may
be predictive in nature.  The authors of
this study noted that the controls were not matched by gender nor by body
mass.  It would be interesting to follow
the cohort of 227 healthy controls to determine whether or not any individuals
with certain genotypes ultimately suffered an ACL injury.  While there is potential, genetic testing to
identify athletes at risk for injury may be years away.  However, this study can inform clinicians
today because it shows the potential for genetic testing and builds on prior
research (see related posts below) that indicated that genes that influence the
composition of an ACL may influence the risk of ACL tears. These genetic risk
factors may also help explain some of the reasons – besides biomechanical and neuromuscular
reasons – why individuals with an ACL injury are at risk for contralateral ACL
injuries.  It may be worth discussing with
a patient that his/her risk for contralateral ACL injury may be related to
biomechanics, neuromuscular control, and possibly genetics. This area of
genetics research should also cause us to wonder whether there are ways we can
improve the composition of native or reconstructed ACLs.

Questions for Discussion:  Do
you foresee the utilization of genotypes to make informed clinical decisions
within your future career?  If you knew
someone had a genotype that made them more susceptible to an injury, what
clinical course of action might you take?

Written
by:
Nicole Cattano
Reviewed
by: Jeffrey Driban

Related Posts:


Rahim, M., Gibbon, A., Hobbs, H., van der Merwe, W., Posthumus, M., Collins, M., & September, A. (2014). The association of genes involved in the angiogenesis-associated signaling pathway with risk of anterior cruciate ligament rupture Journal of Orthopaedic Research, 32 (12), 1612-1618 DOI: 10.1002/jor.22705