Tenascin-C-Matrix Metalloproteinase-3 Phenotype and the Risk of Tendinopathy in High-Performance Athletes: A Case–Control Study
Lucas Rafael Lopes,
Marcus Vinícius Galvão Amaral,
Rodrigo Araujo Goes,
Valéria Tavares,
Francisca Dias,
Rui Medeiros,
Daniel Escorsim Machado,
Jamila Alessandra Perini
Affiliations
Lucas Rafael Lopes
Research Laboratory of Pharmaceutical Science (LAPESF), Rio de Janeiro State University (UERJ), Av. Manuel Caldeira de Alvarenga, 1203—Campo Grande, Rio de Janeiro 23070-200, RJ, Brazil
Marcus Vinícius Galvão Amaral
Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro 20940-070, RJ, Brazil
Rodrigo Araujo Goes
Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro 20940-070, RJ, Brazil
Valéria Tavares
Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto CCC), 4200-072 Porto, Portugal
Francisca Dias
Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto CCC), 4200-072 Porto, Portugal
Rui Medeiros
Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto CCC), 4200-072 Porto, Portugal
Daniel Escorsim Machado
Research Laboratory of Pharmaceutical Science (LAPESF), Rio de Janeiro State University (UERJ), Av. Manuel Caldeira de Alvarenga, 1203—Campo Grande, Rio de Janeiro 23070-200, RJ, Brazil
Jamila Alessandra Perini
Research Laboratory of Pharmaceutical Science (LAPESF), Rio de Janeiro State University (UERJ), Av. Manuel Caldeira de Alvarenga, 1203—Campo Grande, Rio de Janeiro 23070-200, RJ, Brazil
Background/Objectives: Tendon structure is predominantly composed of the extracellular matrix (ECM), and genetic variants in non-collagenous ECM components may influence susceptibility to tendinopathy. We investigated the potential influence of single nucleotide polymorphisms (SNPs) in fibrillin-2 (FBN2), tenascin-C (TNC), and matrix metalloproteinase-3 (MMP3) on the tendon regeneration failure phenotype and impact on the susceptibility to tendinopathy in Brazilian high-performance athletes. Methods: This case–control study was conducted with 397 high-performance athletes from different sports modalities (197 tendinopathy cases and 200 controls), and they were analyzed by validated TaqManTM SNP genotyping assays of the SNPs FBN2 (rs331079), TNC (rs2104772), and MMP3 (rs591058). Results: Out of the 197 tendinopathy cases, 63% suffered from chronic tendon pain and 22% experienced more than three episodes of disease manifestation. The TNC-rs2104772-A allele was significantly associated with tendinopathy (OR: 1.4; 95% CI: 1.1–1.8), while athletes carrying the MMP3-rs591058-T allele were linked to an increased risk of more episodes of disease manifestation (OR: 1.7; 95% CI: 1.1–2.8). The TNC-MMP3 tendon regeneration failure phenotype (TNC-A/MMP3-T) was associated with an increased risk of tendinopathy (OR: 1.4; 95% CI: 1.1–2.0) and episodes of disease manifestation (OR: 2.0; 95% CI: 1.2–3.5). Athletes with tendinopathy who had the TNC-A/MMP3-T interaction were more prone to experiencing more than three disease exacerbations (OR: 4.3; 95% CI: 1.8–10.5) compared to TNC-A/TNC-C. Conclusions: This study suggests that rs2104772 and rs591058 SNPs could be involved in the tendon regeneration failure phenotype and may influence the molecular mechanism related to the regulation of the tendon ECM during training workload.
