Abrahams Yoonus, Laguette Mary-Jessica, Prince Sharon, Collins Malcolm
UCT/MRC Research Unit for Exercise Science and Sports Medicine, Newlands, South Africa.
Ann Hum Genet. 2013 May;77(3):204-14. doi: 10.1111/ahg.12013. Epub 2013 Jan 24.
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.
COL5A1基因编码V型胶原蛋白的α1链，它是肌腱、韧带和其他结缔组织中纤维组装的重要调节因子。功能性COL5A1 3'-非翻译区（UTR）内的一个多态性位点（rs12722）已被证明与慢性跟腱病和其他运动相关表型有关。COL5A1 3'-UTR包含几个假定的顺式作用元件，包括一个功能性的Hsa-miR-608结合位点。本研究的目的是确定COL5A1 3'-UTR功能区域内或MIR608基因中以前未被表征的多态性是否与慢性跟腱病有关。还研究了这些COL5A1 3'-UTR多态性对3'-UTR预测的mRNA二级结构的影响。对160名白种人慢性跟腱病患者和342名对照参与者进行了COL5A1 3'-UTR标记rs71746744、rs16399和rs1134170以及MIR608内标记rs4919510的基因分型。所有四个遗传标记均与慢性跟腱病独立相关。COL5A1多态性似乎改变了3'-UTR预测的二级结构。我们认为二级结构在COL5A1 mRNA稳定性的调节中起作用，进而影响V型胶原蛋白的产生。
