Author(s): COLLINS, M., HILL, L., POSTHUMUS, M., Institution: UNIVERSITY OF CAPE TOWN, Country: SOUTH AFRICA, Abstract-ID: 1903

INTRODUCTION:
There is a growing body of evidence suggesting that inherited DNA sequence variants are important intrinsic risk factors that predispose individuals to musculoskeletal injuries. Previous studies have investigated associations between types I, V, VI, XI and XII collagen gene variants and lower-limb tendinopathies and other exercise-associated musculoskeletal phenotypes. These genes encode important structural components of tendons and other connective tissues and have been proposed to influence inter-individual variation in the biomechanical properties of these tissues and, by implication, susceptibility to injury. However, the association of these collagen gene variants with rotator cuff tendinopathy (RCT), and more specifically supraspinatus tendinopathy (SST), has not been extensively investigated. The aim of this study was therefore to investigate the independent associations, as well as hypothesis-driven collagen gene-gene interactions, of COL1A1, COL5A1, COL6A1, COL11A1, COL11A2 and COL12A1 gene variants with RCT in a South African cohort of swimmers, using a case-control genetic association study design.
METHODS:
One hundred and three swimmers (49 females, 54 males) with clinically diagnosed rotator cuff tendinopathy (RCT group) were recruited, of whom 84.5% (n = 87) were diagnosed with supraspinatus tendinopathy (SST subgroup). In addition, 101 apparently healthy swimmers (55 females, 46 males) with no previous history of shoulder pathology (including RCT, trauma, bursitis, or adhesive capsulitis) were recruited as controls (CON group). All participants were unrelated and of self-reported European ancestry. Participants were genotyped for the following collagen gene polymorphisms: COL1A1 rs1800012 (G>T); COL5A1 rs12722 (T>C) and rs10628678 (AGGG>-); COL6A1 rs35796750 (T>C); COL11A1 rs3753841 (T>C) and rs1676486 (C>T); COL11A2 rs1799907 (A>T); and COL12A1 rs970547 (G>A).
RESULTS:
None of the investigated collagen gene variants were independently associated with rotator cuff tendinopathy or supraspinatus tendinopathy. The inferred C-A-(-) haplotype constructed from COL11A1 rs3753841 (T>C), COL11A2 rs1799907 (A>T) and COL5A1 rs10628678 (AGGG>–) was significantly (p = 0.034) under-represented in the SST subgroup (0.4%) compared with the control group (6.0%). However, none of the other inferred haplotypes constructed from (i) the two COL5A1 variants, (ii) the two COL11A1 variants, (iii) the combined COL11A1 and COL11A2 variants, or (iv) all COL11A1, COL11A2 and COL5A1 variants were associated with RCT or SST risk. Similarly, inferred haplotypes constructed from (i) COL5A1 and COL6A1, (ii) COL5A1 and COL12A1, and (iii) COL6A1 and COL12A1 were also not associated with RCT or SST.
CONCLUSION:
Although several collagen gene variants have previously been associated with lower-limb tendinopathies and other exercise-associated musculoskeletal phenotypes, none of the investigated variants were independently associated with modulating the risk of rotator cuff tendinopathy or supraspinatus tendinopathy in this cohort. Only one collagen gene–gene interaction, specifically involving allelic interactions between COL11A1, COL11A2 and COL5A1, was associated with supraspinatus tendinopathy. Future studies should further investigate the potential interaction between the functionally related types V and type XI collagen genes in the aetiology of supraspinatus tendinopathy.