Evaluating the role of anthropometric and genetic risk factors in ACL injury susceptibility across an Australian and South African cohort

Background Anterior cruciate ligament rupture (ACL-R) is a common sports injury influenced by biomechanical, anthropometric, environmental, and genetic factors. Collagen gene polymorphisms have been implicated in ACL-R, with a whole-genome sequencing twin study highlighting COL12A1 rs970547 C>T as a variant of interest. However, the additive impact of the anthropometric traits and COL12A1 on ACL-R susceptibility remains unexplored. Objectives To investigate the additive effect of anthropometric traits and COL12A1 rs970547 C>T on ACL-R susceptibility in an Australian and South African cohort with the a priori hypothesis that female T/T carriers were at an increased risk. Sample and Methods The study included ACL-R cases (Australia n = 354; South Africa n = 252) and controls (Australia n = 84; South Africa n = 232). COL12A1 rs970547 C>T SNP was genotyped using TaqMan® assays. Anthropometric traits were sex-stratified/standardised. Logistic regression and principal component analyses were assessed. Results No significant genetic associations were found for COL12A1 rs970547 C>T in the i) individual/combined and ii) male/female cohorts. PCA revealed clustering of anthropometrics in PC1–PC2, with PC3 being driven exclusively by rs970547 in each cohort. Conclusion No associations were noted between the COL12A1 rs970547 T/T genotype and ACL-R risk. PCA, however, indicated that rs970547 may hold biological significance in ACL-R susceptibility, highlighting the complex interplay of genetic and anthropometric traits.