Polymorphisms and alterations in Gene Expression associated with Rotator Cuff Tear and healing following surgical repair: A Systematic Review.

ABSTRACT Background Rotator cuff tears (RCT) 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 RCT 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 RCT and interprets these findings to enhance the current understanding of RCT pathogenesis, potential treatment regimens and prognostic biomarkers for outcomes post-surgical repair. Methods A systematic search of Embase, PubMed and Web of Science electronic databases was performed. MeSH and Emtree index terms were formulated from the concept terms “Rotator Cuff Tear”, “ Genetics” and “ Human”, and synonyms of these concepts 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 RCT) and controls (without RCT). 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. Results Two hundred and fifty-nine articles were identified with the search. Twenty-six studies were eligible for review. Two studies were considered to be ‘poor quality’, fifteen studies were ‘moderate quality’ and nine studies were ‘high quality’. Analysis of these articles found 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’ for a significant association between RCTs and the genes MMP-3, TNC and ESRRβ. ‘Strong evidence’ was also found for an association between BMP5 upregulation and successful healing post-surgical repair. Conclusion The current 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 RCT, and predicting an individual’s response to surgical repair. Future research could investigate if manipulating these genes, or their associated signaling pathways, can assist in RCT healing, and whether genetic biomarkers could be utilized clinically to predict patient outcomes post RCT surgical repair.