Friday, October 15, 2010

The Latest on Genes and ACL Injuries

A recent study estimates that 100,000-250,000 anterior cruciate ligament (ACL) reconstruction surgeries are performed each year costing between $2 and $6 billion (3). Add to that the personal costs of rehabilitation, lost playing time and potential for developing arthritis later in life. It becomes evident that ACL injures are a major concern. What are the factors that contribute to ACL injuries? Why are women more likely to suffer an ACL tear than men? These questions have puzzled researchers for years. Three new studies published in the British Journal of Sports medicine address possible genetic factors that may increase the risk of injury. Two studies focus on specific genes while the third examines the role of family history.

A research group from the South African Medical Council and the University of Cape Town previously linked the gene COL5A1 with increased risk of ACL tears (SSO LINK). In the two new studies, they have linked two additional genes, COL1A1 and COL12A1 (1,2). They find that athletes with subtle variations in these genes are more likely to have suffered an ACL injury that those without the variations.

What do these genes do and why are they important? All three genes are responsible for producing collagen, the key protein found in connective tissues like ligaments and tendons. In ligaments, collagen is arranged in filaments or fibrils, forming a rope-like structure that is resistant to stretching and tearing. There are at least 19 types of collagen found in humans. Types I and V forms the basic functional unit of the collagen fibrils whereas Type XII is thought to regulate the diameter of the collagen fibril. Along with a few other types, these collagen proteins give the ligament its structural integrity. The COL1A1, COL5A1 and COL12A1 are responsible for producing Type I, V and XII collagen. Any alteration in the genetic regulation of these collagens can affect the ability of the ligament to resist tearing. It is possible that those athletes with the variant genes might have weaker ligaments. Although this is speculative at this time, it is a reasonable possibility.

The third study (3) approached the genetic question from a different perspective. Dr. Timothy Hewett, of the Cincinnati Children’s Hospital and Sports Medicine Biodynamics Center examined twin athletes who had suffered ACL tears. His group measured anatomical aspects of the knee, movement biomechanics and neuromuscular strength and control of the twins. He then compared them to a large group of uninjured subjects. The results indicated a strong familial component of ACL injury risk. They support the idea that a family history of ACL injuries is an important risk factor. Dr. Hewett points out that many traits which raise the risk of ACL injury may be heritable. These include various neuromuscular, biomechanical, anatomic traits.

These three studies provide more support for the notion that an athlete’s genetic makeup plays a role in the susceptibility of ACL injury risk. They also help explain why some ACL injuries seem to “run in the family”.

While genetics may place some athletes at greater risk of ACL tear, it is important point out two key considerations. First, researchers are not sure the extent to which genetics play a role in ACL injuries. It’s not known whether they play a major role or only a minor one. More research is needed. Second, having certain genetic does not necessarily mean that the athlete will get injured. The new ACL injury prevention programs can greatly lower the overall risk of injury and possibly offset any genetic risks. All athletes, not just those with a family history of injury should focus on improving strength, balance, agility and flexibility along with developing proper techniques of stopping, landing and cutting. These programs have been shown to be very effective in reducing the risk and incidence of ACL injury in athletes, especially female athletes (SSO LINK).

While new research indicates possible genetic factors in ACL injury risk, strategies are available to help athletes avoid this costly and devastating injury.

1. Collins M, Posthumus M, Schwellnus MO (2010) The COL1A1 gene and acute soft tissue ruptures. British Journal of Sports Medicine, doi:10.1136/bjsm.2008.056184.

2. Posthumus M, September AV, O’Cuinneagain D, van der Merwe W, Schwellnus MP, Collins M (2010) The association between the COL12A1 gene and anterior cruciate ligament ruptures, British Journal of Sports Medicine, doi:10.1136/bjsm.2009.060756

3. Hewett TE, Lynch TR, Myer GD, Ford KR, Gwin RC, Heidt RS (2010) Multiple risk factors related to familial predisposition to anterior cruciate ligament injury: fraternal twin sisters with anterior cruciate ligament ruptures. British Journal of Sports Medicine, 44:848-855.