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