Malcolm Collins

The COL5A1 gene and Achilles tendon pathology

Purpose: There is an increase in the incidence of Achilles tendon injuries as a result of the participation in physical activity. It has been suggested that some individuals have a genetic predisposition to Achilles tendon pathology (ATP). The aim of this study was to determine whether the α 1 type V collagen (COL5A1) gene, which encodes for a tendon protein, is associated with the symptoms of ATP.

The Guanine-Thymine Dinucleotide Repeat Polymorphism Within the Tenascin-C Gene Is Associated With Achilles Tendon Injuries

Background Although there is a high incidence of tendon injury as a result of participation in physical activity, the mechanisms responsible for such injuries are poorly understood. Investigators have suggested that some people may have a genetic predisposition to develop tendon injuries; in particular, genes on the tip of the long arm of chromosome 9 might, at least in part, be associated with this condition. The tenascin-C gene, which has been mapped to chromosome 9q32-q34, encodes for a structural component of tendons. Hypothesis The tenascin-C gene is associated with Achilles tendon injury. Study Design Case control study; Level of evidence, 3. Methods A total of 114 physically active white subjects with symptoms of Achilles tendon injury and 127 asymptomatic, physically active white control subjects were genotyped for the guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene. Results A significant difference in the allele frequencies of this polymorphism existed between the 2 groups of subjects (χ2 = 51.0, P =. 001). The frequencies of the alleles containing 12 repeats (symptomatic group, 18.9% vs control group, 10.2%) and 14 repeats (symptomatic group, 9.2% vs control group, 0.8%) were significantly higher in the symptomatic group, while the frequencies of the alleles containing 13 repeats (symptomatic group, 8.8% vs control group, 24.0%) and 17 repeats (symptomatic group, 7.5% vs control group, 20.1%) were significantly lower in this same group. Subjects who were homozygous or heterozygous for the underrepresented alleles (13 and 17 repeats) but who did not possess an overrepresented allele (12 and 14 repeats) may have a lower risk of developing Achilles tendon injuries (odds ratio, 6.2; 95% confidence interval, 3.5-11.0; P <. 001). Conclusions The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with Achilles tendon injury. Alleles containing 12 and 14 guanine-thymine repeats were overrepresented in subjects with tendon injuries, while the alleles containing 13 and 17 repeats were underrepresented. Clinical Relevance Persons who have variants of the tenascin-C gene with 12 and 14 guanine-thymine repeats appear to have a 6-fold risk of developing Achilles tendon injuries.

Weight changes, medical complications, and performance during an Ironman triathlon

Background: Subjects exercising without fluid ingestion in desert heat terminated exercise when the total loss in body weight exceeded 7%. It is not known if athletes competing in cooler conditions with free access to fluid terminate exercise at similar levels of weight loss. Objectives: To determine any associations between percentage weight losses during a 224 km Ironman triathlon, serum sodium concentrations and rectal temperatures after the race, and prevalence of medical diagnoses. Methods: Athletes competing in the 2000 and 2001 South African Ironman triathlon were weighed on the day of registration and again immediately before and immediately after the race. Blood pressure and serum sodium concentrations were measured at registration and immediately after the race. Rectal temperatures were also measured after the race, at which time all athletes were medically examined. Athletes were assigned to one of three groups according to percentage weight loss during the race. Results: Body weight was significantly (p<0.0001) reduced after the race in all three groups. Serum sodium concentrations were significantly (p<0.001) higher in athletes with the greatest percentage weight loss. Rectal temperatures were the same in all groups, with only a weak inverse association between temperature and percentage weight loss. There were no significant differences in diagnostic indices of high weight loss or incidence of medical diagnoses between groups. Conclusions: Large changes in body weight during a triathlon were not associated with a greater prevalence of medical complications or higher rectal temperatures but were associated with higher serum sodium concentrations.

The COL5A1 Gene Is Associated With Increased Risk of Anterior Cruciate Ligament Ruptures in Female Participants

Background Anterior cruciate ligament ruptures, especially to young female athletes, are a cause of major concern in the sports medicine fraternity. The major structural constituents of ligaments are collagens, specifically types I and V. Recently, the gene that encodes for the α1 chain of type I collagen (COL1A1) has been shown to be associated with an increased risk of cruciate ligament ruptures. The COL5A1 gene, which encodes for the α1 chain of type V collagen, has been shown to be associated with Achilles tendon injuries. Purpose The study was conducted to determine (1) if 2 sequence variants (BstUI and DpnII restriction fragment length polymorphisms [RFLPs]) within the COL5A1 gene are associated with an increased risk of anterior cruciate ligament ruptures, and (2) if there were any gender-specific positive associations between the 2 COL5A1 sequence variants and risk of anterior cruciate ligament ruptures. Study Design Case control study; Level of evidence, 3. Methods A total of 129 white participants (38 women) with surgically diagnosed anterior cruciate ligament ruptures and 216 physically active control participants (84 women) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the COL5A1 BstUI and DpnII RFLPs. Results There was a significant difference in the BstUI RFLP genotype frequency between the anterior cruciate ligament rupture and physically active control groups among the female participants, but not the male participants. The CC genotype in the female participants was significantly underrepresented in the anterior cruciate ligament rupture group compared with the controls (27.4% vs 5.6%; odds ratio = 6.6; 95% confidence interval, 1.5–29.7; P = .006). There were no differences in the DpnII RFLP genotype distributions between the anterior cruciate ligament rupture and physically active control groups. Conclusion The CC genotype of the COL5A1 BstUI RFLP was underrepresented in female participants with anterior cruciate ligament ruptures. Clinical Relevance This is the first study to show that there is a specific genetic risk factor associated with risk of anterior cruciate ligament ruptures in female athletes.

Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations

Objectives: A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathy in a South African population. The aim of this case–control genetic association study was to investigate the BstUI and DpnII restriction fragment length polymorphisms (RFLP) in a second population from Australia and to identify a predisposing haplotype for Achilles tendinopathy in both populations. Methods: 85 Australian and 93 South African patients with tendinopathy, as well as 210 Australian and 132 white South African control subjects were genotyped for the BstUI (rs12722) and DpnII (rs13946) RFLP, as well as markers rs10858286, rs3196378, rs11103544, rs4504708 and rs3128575. Results: The BstUI RFLP (p<0.001) and marker rs3196378 (p = 0.016) were associated with chronic Achilles tendinopathy in Australian subjects. Individuals within both populations with a CC genotype for the BstUI RFLP had a significantly decreased risk of developing tendinopathy versus any other genotypes (Australian odds ratio 0.42, 95% CI 0.20 to 0.86, p = 0.017). The TC inferred haplotype (rs12722, rs3196378) was found to be overrepresented (global p = 0.008) in the South African tendinopathy group compared with all other haplotypes. Conclusion: The BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and a region within the COL5A1 3′ untranslated region may predispose individuals to an increased risk of developing chronic Achilles tendinopathy.

What makes champions? A review of the relative contribution of genes and training to sporting success

Elite sporting performance results from the combination of innumerable factors, which interact with one another in a poorly understood but complex manner to mould a talented athlete into a champion. Within the field of sports science, elite performance is understood to be the result of both training and genetic factors. However, the extent to which champions are born or made is a question that remains one of considerable interest, since it has implications for talent identification and management, as well as for how sporting federations allocate scarce resources towards the optimisation of high-performance programmes. The present review describes the contributions made by deliberate practice and genetic factors to the attainment of a high level of sporting performance. The authors conclude that although deliberate training and other environmental factors are critical for elite performance, they cannot by themselves produce an elite athlete. Rather, individual performance thresholds are determined by our genetic make-up, and training can be defined as the process by which genetic potential is realised. Although the specific details are currently unknown, the current scientific literature clearly indicates that both nurture and nature are involved in determining elite athletic performance. In conclusion, elite sporting performance is the result of the interaction between genetic and training factors, with the result that both talent identification and management systems to facilitate optimal training are crucial to sporting success.

Weight changes, sodium levels, and performance in the South African Ironman Triathlon.

ObjectiveTo establish relationships between body weight changes and serum sodium during and after an Ironman Triathlon, and postrace fluid status and rectal temperature, including the incidence of hyponatremia. DesignDescriptive research. SettingThe 2000 South African Ironman Triathlon, in which each athlete swam 3.8 km, cycled 180 km, and ran 42.2 km. ParticipantsAll entrants in the race were invited to participate in the study. MethodsAthletes were weighed at registration, immediately prerace, immediately postrace, and 12 hours later. Blood samples were drawn at registration and immediately postrace. Rectal temperatures were measured postrace. ResultsStarting body weight was significantly related to total finishing time (r = 0.27) and to cycling (r = 0.20) and running (r = 0.28) time. Body weight decreased significantly (p < 0.0001) during the race and had not returned to prerace values 12 hours later (p < 0.0001). Percentage change in body weight was unrelated to postrace rectal temperatures and inversely related to the postrace serum sodium concentrations (r = −0.45). Postrace serum sodium concentrations fell within a normal distribution (141.8 ± 3.1 mmol.L−1, mean ± SD) and were negatively correlated to overall triathlon time (r = −0.22). Three sodium values (0.6%) were below 135 mmol.L−1. Percentage change in body weight was unrelated to time in the marathon leg. ConclusionsPercentage change in body weight was linearly related to postrace serum sodium concentrations but unrelated to postrace rectal temperature or performance in the marathon. There was no evidence that in this study, more severe levels of weight loss or dehydration were related to either higher body temperatures or impaired performance.

Variants within the MMP3 gene are associated with Achilles tendinopathy: possible interaction with the COL5A1 gene

Objectives: Sequence variation within the COL5A1 and TNC genes are known to associate with Achilles tendinopathy. The primary aim of this case-control genetic association study was to investigate whether variants within the matrix metalloproteinase 3 (MMP3) gene also contributed to both Achilles tendinopathy and Achilles tendon rupture in a Caucasian population. A secondary aim was to establish whether variants within the MMP3 gene interacted with the COL5A1 rs12722 variant to raise risk of these pathologies. Methods: 114 subjects with symptoms of Achilles tendon pathology and 98 healthy controls were genotyped for MMP3 variants rs679620, rs591058 and rs650108. Results: As single markers, significant associations were found between the GG genotype of rs679620 (OR = 2.5, 95% CI 1.2 to 4.90, p = 0.010), the CC genotype of rs591058 (OR = 2.3, 95% CI 1.1 to 4.50, p = 0.023) and the AA genotype of rs650108 (OR = 4.9, 95% CI 1.0 to 24.1, p = 0.043) and risk of Achilles tendinopathy. The ATG haplotype (rs679620, rs591058, and rs650108) was under-represented in the tendinopathy group when compared to the control group (41% vs 53%, p = 0.038). Finally, the G allele of rs679620 and the T allele of COL5A1 rs12722 significantly interacted to raise risk of AT (p = 0.006). No associations were found between any of the MMP3 markers and Achilles tendon rupture. Conclusion: Variants within the MMP3 gene are associated with Achilles tendinopathy. Furthermore, the MMP3 gene variant rs679620 and the COL5A1 marker rs12722 interact to modify the risk of tendinopathy. These data further support a genetic contribution to a common sports related injury.

Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant

Background: Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury is not yet fully understood. Recently, the gene encoding for the α1 chain of type I collagen (COL1A1) has been shown to be associated with cruciate ligament ruptures and shoulder dislocations. Objective: To determine whether the functional Sp1 binding site polymorphism within intron 1 of the COL1A1 gene is associated specifically with ACL ruptures in an independent population. Methods: 117 Caucasian participants with surgically diagnosed ACL ruptures, and 130 Caucasian physically active controls without any history of previous ligament or tendon injuries were recruited for this case–control genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012). Results: The rare TT genotype was significantly (p = 0.031, OR = 0.08, 95% CI <0.01 to 1.46) under-represented in the ACL group (0 out of 117, 0%), compared with the controls (6 out of 130, 4.6%). Conclusion: The TT genotype of the COL1A1 Sp1 binding site polymorphism was significantly under-represented in South African participants with ACL ruptures. We propose that this sequence variant be the first specific genetic element to be included in multifactorial models developed to understand the aetiology and risk factors for ACL rupture.

Tendon and ligament injuries: the genetic component

Tendons and ligaments within the upper and lower limbs are some of the more common sites of musculoskeletal injuries during physical activity. Several extrinsic and intrinsic factors have been shown to be associated with these injuries. More recently, studies have suggested that there is also, at least in part, a genetic component to the Achilles tendon, rotator cuff and anterior cruciate ligament injuries. However, specific genes have not been suggested to be associated with rotator cuff or anterior cruciate ligament injuries. Sequence variants of the tenascin C (TNC) gene, on the other hand, have been shown to be associated with Achilles tendinopathies and Achilles tendon ruptures, whereas a variant of the collagen V α 1 (COL5A1) gene has also been shown to be associated with Achilles tendinopathies. Both genes encode for important structural components of tendons and ligaments. The COL5A1 gene encodes for a component of type V collagen, which has an important role in regulating collagen fibre assembly and fibre diameters. The TNC gene, on the other hand, encodes for TNC, which regulates the tissue’s response to mechanical load. To date, only variants in two genes have been shown to be associated with Achilles tendon injuries. In addition, although specific genes have not been identified, investigators have suggested that there is also a genetic component to both rotator cuff and anterior cruciate ligament injuries. In future, specific genotypes associated with increased risk of injury to specific tendons and ligaments can prevent these injuries by identifying individuals at higher risk.