Summary
Variants within extracellular matrix genes are associated with knee joint laxity measurements, possibly by affecting the change of ligament length during movement.
Abstract
Joint laxity and specifically knee joint laxity is affected by both intrinsic and extrinsic risk factors. Variants within collagen encoding genes have recently been included as an intrinsic factor. Rare mutations in collagen as well as other extracellular matrix genes have also been reported to cause heritable connective tissue disorders, which include joint hypermobility as a common clinical feature. Therefore, the purpose of this study was to explore whether variants within the COL12A1, COL27A1 and TNC genes are associated with measurements of knee joint laxity or changes in ligament length during external-internal tibial rotation.
A series of knee joint laxity assessments (genu recurvatum, anterior-posterior tibial displacement and rotational knee laxity) of the dominant and non-dominant legs were carried out for 114 participants. Using an OpenSim discrete elements knee model, ligament length changes during knee rotation testing were computed. Participants were genotyped for COL12A1 (rs970547), COL27A1 (rs2567706, rs2241671 and 2567705) and TNC (rs1061494, rs1138545, and rs2104772).
TNC rs1061494 C allele (P < 0.01) was independently associated with increased external laxity, internal laxity and slack. Similarly, the TNC rs1061494 C allele (P<0.01), together with sex (P<0.05), height (P<0.05) and/or body mass (P<0.05) were significant predictors of the external-internal rotational measurements in multiple linear regression models. Additionally, the A-T (P=0.001) and A-C (P=0.002) allele-allele combinations constructed from COL12A1 rs970547 and TNC rs1061494 were associated with low and high internal laxity measurements. The TNC rs1061494 C allele (P<0.05) was associated with larger length changes in a number of the MCL bundles, the LCL as well as a PCL bundle. The COL12A1 rs970547 G allele (P<0.05) was associated with larger length changes in a number of the MCL bundles.
The study findings suggest that variants within extracellular matrix genes may regulate knee joint laxity, possibly by affecting the change of ligament length during movement. Interestingly, in the genes containing a stretch responsive enhancer region, the effect was noted in the dominant leg. These findings may help improve our understanding of the effects of genetic variation on exercise-related phenotypes such as ACL rupture.