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COL5A1 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.
Annals of Human Genetics – Wiley
Published: Jan 1, 2013
Keywords: ; ; ; ; ;
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