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abstract:
Original paper
A novel combination of genomic loci in ITGB2, COL5A1 and
VEGFA associated with anterior cruciate ligament rupture
susceptibility: insights from Australian, Polish, Swedish,
and South African cohorts
Senanile B. Dlamini
1, 2
,
Christian D. Bope
12, 13, 14
,
Emile R. Chimusa
15, 16
,
Mary-Jessica N. Laguette
1, 2, 17
,
Malcolm Collins
1, 2, 17
,
Alison V. September
1, 2, 17
- Division of Physiological Sciences, Department of Human Biology, University of Cape Town, Anatomy Building, Level 5,
Anzio Road, Observatory, Cape Town, South Africa
- Health through Physical Activity Lifestyle and Sport Research Centre (HPALS), Division of Physiological Sciences, Department
of Human Biology, 3rd Floor, Sports Science Institute Building, Boundary Road, Newlands, 7701, South Africa
- Division of Emergency Medicine, Department of Family, Community and Emergency Care, University of Cape Town, F51 Old
Main Building, Groote Schuur Hospital 7700, Cape Town, South Africa
- Faculty of Physical Education, Gdańsk University of Physical Education and Sport, Gdańsk, Poland
- Faculty of Physiotherapy, Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland
- Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
- Australian Regenerative Medicine Institute (ARMI), Faculty of Medicine, Nursing and Health Sciences, Monash University,
Victoria, Australia
- OrthoSport Victoria Research Unit, Epworth Healthcare, Victoria, Australia
- School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, Australia
- Department of Mathematics and Computer Science, Faculty of Sciences, University of Kinshasa, Kinshasa, Democratic
Republic of Congo
- Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town,
South Africa
- Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway
- Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne and
Wear, United Kingdom
- Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town,
South Africa
- International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine
Biol Sport. 2026;43:3–20
Online publish date: 2025/07/16
PlumX metrics:
Integrin complexes facilitate cell communication, playing a role in ligament homeostasis. ITGB2 rs2230528 (C/T) wasimplicated in anteriorcruciate ligament rupture (ACL) risk in a South African cohort. Identifying biologically significant DNA signatures in the predisposition to ACL rupture risk remains important towards understanding mechanisms of ACL ruptures. ITGB2 is essential for the activation of important biological pathways regulated by structural components such as collagens and biomechanical components such as vasculo-endothelial growth factors. This study tested the association of (i) ITGB2 rs2230528 and (ii) allele-allele combinations of ITGB2’s network partners (COL5A1 rs12722 C/T, VEGFA rs699947 C/A and VEGFA rs2010963 G/C) with ACL rupture risk. The genetic study was conducted in a combined cohort [n=1279: uninjured controls (CON), n=548; ACL ruptures (ACL), n=731; subgroup with non-contact mechanism of ACL ruptures (NON, n=425)] recruited from Australia, Poland, Sweden and South Africa. The combined cohort, rs2230528 TT (best fit model) was significantly over-represented in the ACL (p=8.00×10−8; OR:3.21; 95% CI:2.10–4.89, AIC=1549) and NON (p=1.59×10−6; OR:3.11; 95% CI:1.97–4.91, AIC=1191) groups compared to CON. ITGB2 rs2230528-COL5A1 rs12722-VEGFA rs699947-VEGFA rs2010963, the C-C-A-G and C-T-C-G combinations were significantly associated with reduced ACL risk. This study provided additional evidence highlighting ITGB2 as potentially being associated with ACL ruptures even though the gene-gene combinations had a small effect size. Integrins containing the b2 subunit together with its key extracellular matrix components (type V collagen and VEGFA) are potential therapeutic targets for ACL ruptures and potentially other connective tissue-related conditions.
keywords:
Biomedical knowledge graph, Genetic association study, Cell signalling, Extracellular Matrix Organization pathway, Integrin protein complex
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