Polymorphisms and alterations in gene expression associated with rotator cuff tear and healing following surgical repair: a systematic review

Rotator cuff tears (RCTs) are a common cause of shoulder disability, yet both conservative and surgical treatment strategies can lead to poor results in some patient populations. Enhanced understanding of the genetic processes associated with RCTs can assist in the development of more effective management options and help predict individual responses to surgical treatment. This systematic review analyzes the current literature on the genetic footprint associated with RCTs and interprets these findings to enhance the current understanding of RCT pathogenesis, potential treatment regimens, and prognostic biomarkers of outcomes after surgical repair.

A systematic search of the Embase, PubMed, and Web of Science electronic databases was performed. Medical Subject Headings (MeSH) and Emtree index terms were formulated from the concept terms "rotator cuff tear," "genetics," and "human," and synonyms of these concepts were applied to the Web of Science search. Articles were screened against predefined inclusion and exclusion criteria. Eligible studies compared gene expression patterns and genetic polymorphisms between cases (with RCTs) and controls (without RCTs). Quality assessment was performed with studies being rated as high, moderate, or poor quality. A modified best-evidence synthesis was applied, and studies were determined to be of strong, moderate, or limited evidence.

The search identified 259 articles. Of these studies, 26 were eligible for review. Two studies were considered poor quality; 15 studies, moderate quality; and 9 studies, high quality. Analysis of these articles found that RCTs were associated with alterations in genes that code for the extracellular matrix, cell apoptosis, immune and inflammatory responses, and growth factor pathways. In particular, there was strong evidence of a significant association between RCTs and the genes MMP3, TNC, and ESRRB. Strong evidence of an association between BMP5 upregulation and successful healing after surgical repair was also found.

This review provides strong evidence of an genetic association with RCTs. The genotype and gene expression patterns detailed within this review can assist in deciphering the biological mechanisms resulting in RCTs, as well as predicting an individual's response to surgical repair. Future research could investigate whether manipulating these genes-or their associated signaling pathways-could assist in RCT healing and whether genetic biomarkers could be used clinically to predict patient outcomes after surgical repair of RCTs.