The COL5A1 gene, ultra-marathon running performance, and range of motion.
ABSTRACT Endurance running performance is a multifactorial phenotype that is strongly associated with running economy. Sit and reach range of motion (SR ROM) is negatively associated with running economy, suggesting that reduced SR ROM is advantageous for endurance running performance. The COL5A1 gene has been associated with both endurance running performance and SR ROM in separate cohorts. The aim of this study was to investigate whether COL5A1 is associated with ultra-marathon running performance and whether this relationship could be partly explained by prerace SR ROM.
Seventy-two runners (52 male, 20 female) were recruited from the 56 km Two Oceans ultra-marathon and were assessed for prerace SR ROM. The cohort was genotyped for the COL5A1 BstUI restriction fragment length polymorphism, and race times were collected after the event.
Participants with a TT genotype (341 ± 41 min, N = 21) completed the 56 km Two Oceans ultra-marathon significantly (P = 0.014) faster than participants with TC and CC genotypes (365 ± 39 min, N = 50). The COL5A1 genotype and age accounted for 19% of performance variance. When the cohort was divided into performance and flexibility quadrants, the T allele was significantly (P = 0.044) over-represented within the fast and inflexible quadrant.
The COL5A1 genotype was found to be significantly associated with performance in a 56 km ultra-endurance run. This study confirms previous findings and it furthers our understanding of the relationships among ROM, COL5A1, and endurance running performance. We continue to speculate that the COL5A1 gene alters muscle-tendon stiffness.
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ABSTRACT: To explore whether genetic susceptibility is a potential risk factor for superficial digital flexor (SDF) tendinopathy in Thoroughbred (TB) racehorses. To identify informative single nucleotide polymorphisms (SNPs) that capture genetic diversity across a range of candidate genes and to investigate, in a case-control study, their association with SDF tendinopathy in UK National Hunt (NH) Thoroughbred racehorses in training. Case-control candidate gene association study. This study used in silico genome assembly and DNA sequencing to screen candidate genes for SNPs. Seven candidate genes were selected using a hypothesis-driven approach; tenascin C (TNC), collagen type 1 alpha 1 (COL1A1), collagen type 5 alpha 1 (COL5A1), matrix metalloproteinase type 3 (MMP3), matrix metalloproteinase type 13 (MMP13), fibromodulin (FMOD) and cartilage oligomeric matrix protein (COMP). SNPs were validated in DNA isolated from 48 TB racehorses and used to genotype 270 racehorses with SDF tendinopathy and 270 yard-matched controls. Genotyping of cases and controls was performed using SNaPshot™. Racehorses heterozygous for the TNC BIEC2-696469 polymorphism were less likely to have SDF tendinopathy than racehorses homozygous for the wild-type allele (OR 0.56, CI 0.36-0.85, P = 0.01). This finding remained significant after adjustment for age and racing background (OR 0.57, CI 0.36-0.92, P = 0.03). Racehorses homozygous for the novel COL5A1 COL5A1_01 variant allele were nearly 3 times more likely to have SDF tendinopathy than those homozygous for the wild-type allele (OR 2.82, CI 1.25-6.35, P = 0.01); this association remained significant after adjustment for age and racing background (OR 2.77, CI 1.18-6.53, P = 0.03). Results suggest that sequence variants in TNC and COL5A1 genes are associated with SDF tendinopathy in TB racehorses and in future genetic markers may be used to identify horses at risk of SDF tendinopathy.Equine Veterinary Journal 07/2013; · 2.29 Impact Factor
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ABSTRACT: The biological mechanisms involved in non-contact musculoskeletal soft tissue injuries (NCMSTI) are poorly understood. Genetic risk factors may be associated with susceptibility to injuries, and may exert marked influence on recovery times. Data on type and degree of injury and recovery time were collected in 73 male professional soccer players (43 White, 11 Black Africans and 19 Hispanics) who suffered total of 242 injuries (203 muscle, 24 ligament, and 15 tendon injuries). One single nucleotide polymorphism (SNPs) in the following genes were analyzed : Elastin (ELN); Titin (TTN); SRY-related HMG-box (SOX15); Insulin-like growth factor 2 (IGF2); Chemokine, CC motif, ligand 2 (CCL2); Collagen type 1 alpha 1(COL1A1); Collagen type 5 alpha 1 (COL5A1), and Tenascin C (TNC). There was evidence of a statistically significant association between the degree of injury and the IGF2 genotype (P=0.034). In addition, there was evidence of a statistically significant association between the degree of muscle injury and CCL2 (P=0.026) Finally, there was evidence of a statistically significant association between ELN and degree of injury (p=0.009) and recovery time (P=0.043). There was no evidence of a statistically significant association between any of the genes studied and degree of injury or recovery time for tendon injuries. SNPs in the IGF2, CCL2, and ELN genes may be associated to the degree and recovery time of NCMSTI.BMC Musculoskeletal Disorders 07/2013; 14(1):221. · 1.88 Impact Factor
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ABSTRACT: COL5A1 encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, ligaments and other connective tissues. A polymorphism (rs12722) within the functional COL5A1 3'-untranslated region (UTR) has been shown to associate with chronic Achilles tendinopathy and other exercise-related phenotypes. The COL5A1 3'-UTR contains several putative cis-acting elements including a functional Hsa-miR-608 binding site. The aim of this study was to determine whether previously uncharacterized polymorphisms within a functional region of the COL5A1 3'-UTR or the MIR608 gene are associated with chronic Achilles tendinopathy. The effect of these COL5A1 3'-UTR polymorphisms on the 3'-UTR predicted mRNA secondary structure was also investigated. One hundred and sixty Caucasian chronic Achilles tendinopathic and 342 control participants were genotyped for the COL5A1 3'-UTR markers rs71746744, rs16399 and rs1134170, as well as marker rs4919510 within MIR608. All four genetic markers were independently associated with chronic Achilles tendinopathy. The COL5A1 polymorphisms appear to alter the predicted secondary structure of the 3'-UTR. We propose that the secondary structure plays a role in the regulation of the COL5A1 mRNA stability and by implication type V collagen production.Annals of Human Genetics 01/2013; · 2.22 Impact Factor