Ewelina Lulińska-Kuklik1, Masouda Rahim2, Waldemar Moska1, Ewelina Maculewicz3, Mariusz Kaczmarczyk1, Agnieszka Maciejewska-Skrendo4, Krzysztof Ficek5, Pawel Cieszczyk6, Alison V September7, Marek Sawczuk1. 1. Faculty of Tourism and Recreation, Gdansk University of Physical Education and Sport, Poland. 2. Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa. 3. Applied Physiology Unit, Military Institute of Hygiene and Epidemiology, Poland. 4. Faculty of Physical Education, Gdansk University of Physical Education and Sport, Poland. 5. Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education in Katowice, Poland. 6. Applied Physiology Unit, Military Institute of Hygiene and Epidemiology, Poland; Faculty of Physical Education, Gdansk University of Physical Education and Sport, Poland. 7. Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa. Electronic address: Alison.September@uct.ac.za.
Abstract
OBJECTIVES: Anterior cruciate ligament rupture (ACLR) is a common and severe knee injury which typically occurs as a result of sports participation, primarily via a non-contact mechanism. A number of extrinsic and intrinsic risk factors, including genetics, have been identified thus far. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) play a crucial role in extracellular matrix remodeling of ligaments and therefore the genes encoding MMPs and TIMPs are plausible candidates for investigation with ACL rupture risk. DESIGN: A case-control genetic association study was conducted on 229 (158 male) individuals with surgically diagnosed primary ACLR, ruptured through non-contact mechanisms and 192 (107 male) apparently healthy participants (CON) without any history of ACLR. All participants were physically active, unrelated, self-reported Caucasians. METHODS: All participants were genotyped for four single nucleotide polymorphisms (SNP): MMP3 (rs591058C/T, rs679620 G/A), MMP8 (rs11225395C/T), and TIMP2 (rs4789932 G/A) using standard PCR assays. Gene-gene interactions were inferred. Single-locus association analysis was conducted using the Chi-square test. SNP-SNP interaction effects were analysed using multifactor dimensionality reduction (MDR) method. RESULTS: Genotype frequencies did not significantly differ between cases and controls, however, the MMP3 rs679620 G and rs591058C alleles were significantly overrepresented in cases compared to controls (p=0.021, OR=1.38, 95% CI: 1.05-1.81). CONCLUSIONS: These results support the hypothesis that genetic variation within MMP3 contributes to inter-individual susceptibility to non-contact ACLR. However, these results need to be explored further in larger, independent sample sets.
OBJECTIVES: Anterior cruciate ligament rupture (ACLR) is a common and severe knee injury which typically occurs as a result of sports participation, primarily via a non-contact mechanism. A number of extrinsic and intrinsic risk factors, including genetics, have been identified thus far. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) play a crucial role in extracellular matrix remodeling of ligaments and therefore the genes encoding MMPs and TIMPs are plausible candidates for investigation with ACL rupture risk. DESIGN: A case-control genetic association study was conducted on 229 (158 male) individuals with surgically diagnosed primary ACLR, ruptured through non-contact mechanisms and 192 (107 male) apparently healthy participants (CON) without any history of ACLR. All participants were physically active, unrelated, self-reported Caucasians. METHODS: All participants were genotyped for four single nucleotide polymorphisms (SNP): MMP3 (rs591058C/T, rs679620 G/A), MMP8 (rs11225395C/T), and TIMP2 (rs4789932 G/A) using standard PCR assays. Gene-gene interactions were inferred. Single-locus association analysis was conducted using the Chi-square test. SNP-SNP interaction effects were analysed using multifactor dimensionality reduction (MDR) method. RESULTS: Genotype frequencies did not significantly differ between cases and controls, however, the MMP3rs679620 G and rs591058C alleles were significantly overrepresented in cases compared to controls (p=0.021, OR=1.38, 95% CI: 1.05-1.81). CONCLUSIONS: These results support the hypothesis that genetic variation within MMP3 contributes to inter-individual susceptibility to non-contact ACLR. However, these results need to be explored further in larger, independent sample sets.