Genetic Factors in Rotator Cuff Pathology, Part 2

In Part 1 of this article, we began looking at genetic factors in rotator cuff pathology and the future implications for sports physical therapists. In Part 2, we explore the influence genetics may have on a person’s recovery after a rotator cuff tear.

In addition to gaining a better understanding of the elaborate cellular signaling associated with rotator cuff tearing, several studies have begun to explore the influence of a person’s genetic profile on the presence of rotator cuff tears in addition to their post-operative recovery after a rotator cuff repair. Here are the highlights of some of these recent studies:

Tashjian et al (2016) completed a genetic analysis on 311 subjects with a full thickness rotator cuff tear. They studied the presence of single nucleotide polymorphisms (SNPs), which are normal variations of a person’s genetic code between individuals, between this group containing a rotator cuff tear and a control database of 3293 individuals. They found that there was a statistically significant association of SNPs within genes of SAP30BP and SASH1, both of which are associated with the apoptotic process. It has previously been proposed that an apoptotic cascade initiating from the hypoxic environment of the supraspinatus tendon contributes to tissue degradation and eventual rotator cuff tears. Tashjian et al suggested that alterations within the SAP30BP and SASH1 genes in individuals experiencing a rotator cuff tear may promote increased protein activity and a subsequent rotator cuff tear in individuals with these SNPs.

A more recent study by Tashjian et al (2016) examined 72 patients undergoing an arthroscopic repair of a full thickness rotator cuff tear. They then completed MRI analysis at least one year post-operatively and detected a 42% re-tear rate. Of the patients who re-tore, 43% displayed a Cho type I lateral failure, where no remaining rotator cuff tissue was present at the insertion site of the greater tuberosity. Patients with a lateral failure were then found to display a statistically significant increased prevalence of an SNP within the estrogen-related receptor beta gene. Researchers did not find any difference in age, supraspinatus muscle quality, or single versus double row repair type in the tears that healed or re-tore. This finding indicates that the genetic profile of a patient may be a stronger predictor of future rotator cuff post-operative re-tearing than some of the traditional factors such as muscle quality or age.

Another area of research regarding re-tear rates with rotator cuff repairs concerns the presence of matrix metalloproteinases (MMPs). MMPs are a family of highly regulated enzymes that are responsible for degrading all components of connective tissue. Excessive expression of MMPs can be deleterious to the rotator cuff tendons and can lead to tissue tearing and re-tearing after a rotator cuff repair.

A study by Gotoh et al (2013) examined 24 patients undergoing a full thickness open rotator cuff repair. At the time of the repair, researchers harvested a 5mm section of the torn tendon, and then analyzed this tissue for gene expression levels. Then, one year post-operatively, a repeat MRI was completed and 25% of patients were found to have a re-tear. Of those patients with a re-tear, there was a statistically significant increase in gene expression of MMP3.

A similar study by Robertson et al (2012) examined 30 patients with a fully torn rotator cuff tendon or a high grade partial tear (>80% torn). An ultrasound was completed >6mo post-operatively and 23% of patients were found to have a re-tear. Of the patients with a re-tear, there was a statistically significant increase in MMP1 and MMP9 gene expression levels compared to the group of patients that healed well. In this study MMP3 was not studied.

These results in concert begin to reveal some of the genetic and cellular markers that may predispose a patient to an initial rotator cuff tear and may subsequently impair healing of a rotator cuff repair. For a rehab specialist, this information may potentially influence the type and rate of post-operative rehabilitation performed on a patient recovering from a rotator cuff repair (Table 1 and 2). Ultimately, the goal would be to help decrease the prevalence of rotator cuff re-tears after a repair to promote improved long-term outcomes following a rotator cuff repair surgery.

Tables from Orth et al. 2017.

References:

Gotoh M, Mitsui Y, Shibata H, et al. Increased matrix metalloprotease-3 gene expression in ruptured rotator cuff tendons is associated with postoperative tendon retear. Knee Surg Sports Traumatol Arthrosc. 2013;21(8):1807-12.

Kokmeyer D, Dube E, Millett PJ. Prognosis driven rehabilitation after rotator cuff repair surgery. Open Orthop J. 2016;10:339-48.

Orth T, Paré J, Froehlich J. Current concepts on the genetic factors in rotator cuff pathology and future implications for sports physical therapists. Int J Sports Phys Ther. 2017;12(2):273-285.

Robertson CM, Chen CT, Shindle MK, et al. Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons. Am J Sports Med. 2012;40(9):1993-2001.

Tashjian RZ, Granger EK, Farnham JM, et al. Genome wide association study for rotator cuff tears identifies two significant single nucleotide polymorphisms. J Shoulder Elbow Surg. 2016;25(2):174-9.

Tashjian RZ, Granger EK, Zhang Y, et al. Identification of a genetic variant with rotator cuff repair healing. J Shoulder Elbow Surg. 2016;25(6):865-72.


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