The interaction of polymorphisms in extracellular matrix genes and underlying miRNA motifs that modulate susceptibility to anterior cruciate ligament rupture.

Objectives: Variants within genes that encode proteins regulating fibrillogenesis such as BGN (rs1126499 C>T, rs1042103 C>T), COL5A1 (rs12722 C>T) and DCN (rs516115 C>T) have been associated with susceptibility to anterior cruciate ligament (ACL) ruptures. A miRNA mediated transcript instability was proposed for the COL5A1 association. The study aims were: (i) to investigate the association of inferred allele combinations across the COL5A1 3'-UTR, BGN and DCN genes with susceptibility to ACL rupture; and (ii) to use an in silico approach to identify miRNA binding sites common to these risk associated allele combinations.

Modulators of the extracellular matrix and risk of anterior cruciate ligament ruptures.

Objectives: The extracellular matrix (ECM) of ligaments continuously undergoes remodelling in order to maintain tissue homeostasis. Several key mediators of ECM remodelling were chosen for investigation in the present study. It is thought that polymorphisms within genes encoding signalling molecules may contribute to inter-individual variation in the responses to mechanical loading, potentially altering risk of injury.

Genes encoding proteoglycans are associated with the risk of anterior cruciate ligament ruptures.

Background: Genetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity of ligaments. Genes encoding proteoglycans are plausible candidates to be investigated for associations with ACL injury susceptibility; polymorphisms within genes encoding the proteoglycans aggrecan (ACAN), biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) were examined.