Polymorphisms within the COL5A1 3'-UTR that alters mRNA structure and the MIR608 gene are associated with Achilles tendinopathy.
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.
UCT/MRC Research Unit for Exercise Science and Sports Medicine, Newlands, South Africa.
Yoonus
Y
Abrahams
Mary-Jessica
MJ
Laguette
Sharon
S
Prince
Malcolm
M
Collins
D020413:3' Untranslated Regions; D000125:Achilles Tendon / Q000473:pathology*; D000328:Adult; D000483:Alleles; D001315:Australia / Q000453:epidemiology; D001665:Binding Sites; D016022:Case-Control Studies; D002908:Chronic Disease; D024062:Collagen Type V / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D052256:Tendinopathy / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics
D020413:3' Untranslated Regions; C530725:COL5A1 protein, human; D024062:Collagen Type V; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger