Investigation of angiogenesis genes with anterior cruciate ligament rupture risk in a South African population

The angiogenesis-signalling pathway is a physiological response after mechanical loading to promote matrix remodelling and thereby maintain tissue homeostasis. Studies have shown increased expression of angiogenic molecules in response to loading and in ruptured ligaments. Recently, polymorphisms within the vascular endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes were associated with risk of anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy in Caucasian study groups. A case-control genetic association study was conducted on 100 controls and 98 participants with surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact mechanism of injury (NON). All participants were genotyped for five functional polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559, rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559 AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00–3.59) in the controls. Furthermore, the GG genotype was significantly under-represented in the male controls compared to the male ACL group (P = 0.018, OR: 2.77, 95% CI: 1.17–6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI: 1.24–8.58). Haplotype analysis implicated the KDR gene in all participants and in male participants separately. Collectively, these results implicate the angiogenesis-signalling pathway as a potentially key biological pathway contributing to ACL injury susceptibility.     

Polymorphisms within the COL5A1 gene and regulators of the extracellular matrix modify the risk of Achilles tendon pathology in a British case-control study

Several genetic loci have been associated with risk of Achilles tendon pathology (ATP) within South African and Australian populations. The aim of this study was, therefore, to evaluate eight previously implicated genetic variants in an independent British population. A total of 130 asymptomatic controls (CON) and 112 participants clinically diagnosed with ATP comprising 87 individuals with chronic Achilles tendinopathy (TEN) and 25 with Achilles tendon ruptures (RUP) were included. All participants were genotyped for variants within the COL5A1, MIR608, IL-1β, IL-6 and CASP8 genes. Primary findings implicated COL5A1 and CASP8. Three inferred allele combinations constructed from COL5A1 rs12722, rs3196378 and rs71746744 were identified as risk modifiers. The T–C–D combination was associated with increased risk of ATP (P = 0.023) and RUP (P < 0.001), the C–A–I combination was associated with increased risk of ATP (P = 0.011), TEN (P = 0.011) and RUP (P = 0.011) and the C–C–D combination was associated with decreased risk of ATP (P = 0.011) and RUP (P = 0.004). The CASP8 rs3834129 DD genotype was associated with decreased risk of TEN (P = 0.020, odds ratio: 0.45, 95% confidence interval: 0.22–0.90) and the CASP8 I–G (rs3834129–rs1045485) inferred allele combination was associated with increased risk of TEN (P = 0.031). This study further highlights the importance of polymorphisms within COL5A1 and CASP8 in the aetiology of ATP.     

ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study

Abstract

We tested the hypothesis that the performance of rapid movements represents body size-independent indices of muscle power. Physical education students (n = 159) were tested on various vertical jump (jump height and average power calculated from the ground reaction force) and muscle strength tests. When non-normalized data were used, a principal components analysis revealed a complex and inconsistent structure where jump height and muscle power loaded different components, while muscle strength and power partially overlapped. When the indices of muscle strength and power were properly normalized for body size, a simple and consistent structure of principal components supported the hypothesis. Specifically, the recorded height and muscle power calculated from the same jumps loaded the same components, separately for the jumps predominantly based on concentric actions and jumps based on a rapid stretch – shortening cycle of the leg extensors. The finding that the performance of rapid movements assesses the same physical ability as properly normalized tests of muscle power could be important for designing and interpreting the results of batteries of physical performance tests, as well as for understanding some basic principles of human movement performance.