Polymorphisms within the COL5A1 3′‐UTR That Alters mRNA Structure and the MIR608 Gene are Associated with Achilles Tendinopathy

Abstract

SummaryCOL5A1 encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, ligaments and other connective tissues. A polymorphism (rs12722) within the functional COL5A1 3 -untranslated region (UTR) has been shown to associate with chronic Achilles tendinopathy and other exercise-related phenotypes. The COL5A1 3 -UTR contains several putative cis-acting elements including a functional Hsa-miR-608 binding site. The aim of this study was to determine whether previously uncharacterized polymorphisms within a functional region of the COL5A1 3 -UTR or the MIR608 gene are associated with chronic Achilles tendinopathy. The effect of these COL5A1 3 -UTR polymorphisms on the 3 -UTR predicted mRNA secondary structure was also investigated. One hundred and sixty Caucasian chronic Achilles tendinopathic and 342 control participants were genotyped for the COL5A1 3 -UTR markers rs71746744, rs16399 and rs1134170, as well as marker rs4919510 within MIR608. All four genetic markers were independently associated with chronic Achilles tendinopathy. The COL5A1 polymorphisms appear to alter the predicted secondary structure of the 3 -UTR. We propose that the secondary structure plays a role in the regulation of the COL5A1 mRNA stability and by implication type V collagen production.

Comparative Gene Approach to the Investigation of SNPs within the Tenascin-C Gene in Achilles Tendon Injury in the Canine Patient

“…The mean age was 7.1 years ± 2.4 (range 2-10 years), and mean weight was 33.1kg ± 7.1 (range 22.7-46.8kg). Breeds affected included Labrador retrievers (14), German shorthair pointers (4), and one each of golden retriever and Munsterlander. There were 6 males (5 neutered, 1 intact) and 14 females (13 spayed, 1 intact) represented (See Table 1).…”

“…Intrinsic risk factors for developing tendinopathy, including genetic variations in chromosome 9, are well documented in humans [4][5][6] . In humans, Achilles tendinopathy has been extensively studied for numerous polymorphisms within several genes and has been found to be associated with polymorphisms in collagen (COL5A1) and the tenascin genes 4,[7][8][9][10][11][12][13][14][15][16] . Tenascin encodes the extracellular matrix tenascin-C glycoprotein, which is expressed during wound healing and remodeling of adult tissues, especially those exposed to high tensile and compressive stress.…”

Different distributions of operative diagnoses for Achilles tendon overuse injuries in Italian and Finnish athletes

“…There is a consensus, that the reasons for tendon pain and degeneration must be elucidated before the tendinopathy problem can be solved. New intrinsic factors have been discovered through genomic research, such as the COL5A1 gene, and extrinsic factors are neither well understood although correlations to tendinopathy exist, such as tendon load 12,27 . This present study promotes two approaches to elucidate AT pathology.…”

Achilles Tendon Injuries in Elite Athletes: Lessons in Pathophysiology from Their Equine Counterparts

“…Developments in genetic profiling techniques over the past 5 to 6 years have resulted in identification of a number of polymorphisms in matrix protein-encoding genes that have association with a higher risk of AT injury. These include genes encoding nonfibrillar collagens (e.g., COL5A1, COL11A2, and COL27A1), an associated microRNA (e.g., MIR608), a procollagen processing enzyme ( procollagen N-propeptidase; ADAMTS14), and tenascin C (TNC; a glycoprotein) (Abrahams et al 2013;El Khoury et al 2013;Hay et al 2013;September et al 2012). Collagen V regulates collagen fibril generation and organization, and tenascin C is involved in cell-matrix interactions.…”