@Article{Dlamini2026,
journal="Biology of Sport",
issn="0860-021X",
volume="43",
number="1",
year="2026",
title="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",
abstract="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.",
author="Dlamini, Senanile B.
and Saunders, Colleen J.
and Cieszczyk, Paweł
and Ficek, Krzysztof
and Häger, Charlotte K.
and Stattin, Eva-Lena
and Nilsson, Kjell G.
and Eynon, Nir
and Feller, Julian A.
and Tirosh, Oren
and Bope, Christian D.
and Chimusa, Emile R.
and Laguette, Mary-Jessica N.
and Collins, Malcolm
and September, Alison V.",
pages="3--20",
doi="10.5114/biolsport.2026.152346",
url="http://dx.doi.org/10.5114/biolsport.2026.152346"
}