The VEGFA gene and anterior cruciate ligament rupture risk in the Caucasian population

Abstract

The aim of the present study was to analyse VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with susceptibility to anterior cruciate ligament rupture (ACLR) in a Polish population. The study included 412 physically active Caucasian participants. The study group consisted of 222 individuals with surgically diagnosed primary ACLR qualified for ligament reconstruction (ACLR group). The control group consisted of 190 apparently healthy participants without any history of ACLR (CON group). Three polymorphisms within the VEGFA (rs699947, rs1570360, and rs2010963) gene were chosen for investigation due to their significance in the angiogenesis signalling pathway and previous associations with risk of ACLRs. Both single-locus and haplotype-based analyses were conducted. No significant differences in the allele and genotype frequency distributions were noted for the rs699947 and rs1570360 polymorphisms. In contrast, rs2010963 was associated with risk of ACLR in the codominant (p=0.047) and recessive model (p=0.017). In the latter, the CC genotype was overrepresented among individuals with ACL rupture (23.4% vs 14.2%, OR=1.85 [1.11-3.08]). Two VEGFA haplotypes were associated with ACLR under the additive (global score=11.39, p=0.022) and dominant model (global score=11.61, p=0.020). The [C;G;G] haplotype was underrepresented in the ACLR group (52.2% vs. 60.3%), whereas the [C;G;C] haplotype was overrepresented (2.9% vs 0.5%). The results obtained suggest a potential correlation between the VEGFA rs2010963 polymorphism and ACLR risk, suggesting that harbouring this specific C allele may be an unfavourable risk factor for a knee injury in Caucasian participants from Poland.

The genetic association with injury risk in male academy soccer players depends on maturity status

“…Ligament and ligament/tendon injury prevalence was also greater for VEGFA rs2010963 CC homozygotes in pre‐PHV ASP, which is in accordance with the finding that CC homozygotes suffer more ACL injuries in professional soccer 19 . While limited to pre‐PHV, our finding supports the association of the VEGFA CC genotype with soccer‐related ligament injury, which may be due to enhanced protein expression and plasma VEGFA concentration in CC homozygotes 20 .…”

VEGFA Promoter Polymorphisms rs699947 and rs35569394 Are Associated With the Risk of Anterior Cruciate Ligament Ruptures Among Indian Athletes: A Cross-sectional Study

“…Angiogenesis-associated signaling is considered a key modulator of fibroblast cytoskeletal matrix remodeling after cyclic mechanical loading during complex sporting maneuvers, with VEGFA having the highest angiogenic potency. 19 Conflicting observations for genomic sequence variants within the VEGF gene have previously been reported for the ACL injury risk 14,19,20 and tendinopathies 18,24 in multiple White populations. Thus, we hypothesized that polymorphisms within the VEGFA promoter region (rs699947 and rs35569394) could be positively associated with the ACL rupture risk in the Indian athletic population.…”

“…34 The VEGF-A isoform has shown the highest angiogenic potency, 19 and one of its promoter SNPs, VEGFA rs699947 (-2578 C>A; 6:43768652), has been linked to a number of pathophysiological conditions, including coronary artery disease, 33 cancer, 18 rheumatoid arthritis, 10 and certain tendinopathies. 14,18,20 VEGFA rs35569394 (18bp I/D; 6:43736418) is an 18-bp insertion/deletion polymorphism located at the À2549 position in the promoter region of the VEGF gene and has been found to be associated with increased angiogenesis in several conditions such as diabetic nephropathy, 1 diabetic retinopathy, 5 and certain types of cancers. 11 Although a potent angiogenic site, the role of rs35569394 (À2549 18bp I/D) has not been investigated in musculoskeletal soft tissue injuries.…”

“…34 The VEGF-A isoform has shown the highest angiogenic potency, 19 and one of its promoter SNPs, VEGFA rs699947 (-2578 C>A; 6:43768652), has been linked to a number of pathophysiological conditions, including coronary artery disease, 33 cancer, 18 rheumatoid arthritis, 10 and certain tendinopathies. 14,18,20…”

Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review

“…Independent and haplotype associations were noted for VEGFA functional variants (rs699947, rs1570360, and rs2010963) with ACL rupture susceptibility [ 172 , 174 , 177 , 178 ] including contrasting associations between ACL rupture and AT susceptibility. For example, the VEGFA rs699947 CC was associated with increased risk of non-contact ACL ruptures [ 174 ] but associated with a reduced risk of AT [ 124 ].…”