Range of motion measurements diverge with increasing age for COL5A1 genotypes

Increased and decreased joint range of motion (ROM) are modifiable risk factors for musculoskeletal soft-tissue injuries. Certain heritable disorders of connective tissue, which have a unifying symptom of joint hypermobility, are caused by mutations within the COL5A1 gene. Furthermore, the COL5A1 BstUI restriction fragment length polymorphism (RFLP) sequence variant is associated with ROM measurements in a mixed injured/uninjured cohort. The association between COL5A1 BstUI RFLP and sit and reach (SR) ROM in an apparently healthy and physically active cohort was investigated. The SR test was performed on 325 white subjects (204 males). Subjects were also genotyped for the BstUI RFLP (C/T) within the 3'-untranslated region of the COL5A1 gene. The COL5A1 BstUI RFLP genotype was associated with SR ROM in older (≥35 years) subjects (TT: 225 ± 96 mm, TC: 245 ± 100 mm, CC: 32 ± 108 mm, N=96, P=0.017). Age and COL5A1 BstUI genotype interacted significantly for SR ROM. Sex and COL5A1 genotype accounted for 22.8% of the variance in SR ROM in the older group. The COL5A1 BstUI RFLP is associated with SR ROM, particularly with increasing age and is an important contributing factor to ROM variation, particularly in older, apparently healthy and physically active individuals.     

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 alpha 1 type V collagen (COL5A1) gene, which encodes for a tendon protein, is associated with the symptoms of ATP. METHODS: One-hundred and eleven Caucasian subjects diagnosed with ATP and 129 Caucasian control (CON) subjects were genotyped for the BstUI and DpnII restriction fragment length polymorphisms (RFLPs) within the COL5A1 gene. RESULTS: There was a significant difference in the allele frequencies of the COL5A1 BstUI RFLP between the ATP and CON subjects (P=0.006). The frequency of the A2 allele was significantly higher in the CON group (29.8%) than in the ATP group (18.0%) (odds ratio of 1.9; 95% confidence interval (CI) 1.3-3.0; P=0.004). This allele had a stronger protective role when only the 72 patients diagnosed with chronic Achilles tendinopathy were analyzed (odds ratio of 2.6; 95% CI 1.5-4.5). CONCLUSIONS: The COL5A1 BstUI RFLP is associated with ATP and more specifically, chronic Achilles tendinopathy. Individuals with an A2 allele of this gene are less likely of developing symptoms of chronic Achilles tendinopathy.     

COL11A1 gene is associated with limbus vertebra in gymnasts

Several studies have shown higher frequencies of radiological abnormalities among gymnasts. Recently, the gene encoding the α1 chain of type XI collagen, (COL11A1) (rs 1676486), was associated with lumbar disc herniation in the Japanese population. We hypothesized that there was a significant relationship between abnormal magnetic resonance imaging (MRI) findings of the lumbar spine and the COL11A1 4603C/T gene polymorphism in collegiate gymnasts. Our study participants included 103 Japanese collegiate gymnasts (70 men and 33 women). Radiological abnormalities were evaluated using T1- and T2-weighted MRI. Genotyping for COL11A1 was performed for all the participants. By using logistic regression analysis, we observed significant associations between limbus vertebra and age (adjusted odds ratio=0.51, 95% confidence interval: 0.27-0.96), sporting experience (adjusted odds ratio=1.49, 95% confidence interval: 1.14-1.94), and a TT genotype (adjusted odds ratio=7.83, 95% confidence interval: 1.33-46.03). We conclude that a TT genotype of COL11A1 polymorphism may be a significant risk factor for limbus vertebra in Japanese collegiate gymnasts.     

TTN genotype is associated with fascicle length and marathon running performance

Titin provides a molecular blueprint for muscle sarcomere assembly, and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus, the aim of this study was to investigate whether the titin (TTN ) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA ; n=137) and marathon personal best time in male marathon runners (MR ; n=141). Fascicle length of the vastus lateralis was assessed in vivo using B‐mode ultrasonography at 50% of muscle length in RA . All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real‐time polymerase chain reaction. Vastus lateralis fascicle length was 10.4% longer in CC homozygotes, those carrying two copies of the C‐allele, than CT heterozygotes (P =.003) in RA . In the absence of any TT homozygotes, reflective of the low T‐allele frequency within Caucasian populations, it is unclear whether fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P =.500), although within the MR group, the T‐allele carriers demonstrated marathon personal best times 2 minutes 25 seconds faster than CC homozygotes (P =.020). These results suggest that the T‐allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men.     

Passive knee joint range of motion is unrelated to the mechanical properties of the patellar tendon

The physiological factors that govern passive joint range of motion (ROM) are poorly understood. The present study investigated the relation between passive knee joint ROM and the mechanical properties of the patellar tendon. Knee joint ROM was assessed in 43 individuals, and the subjects with the greatest ROM (flexible group, n=10) and lowest ROM (inflexible group, n=10) were selected for further analysis. In these groups an overall "lower extremity joint ROM score" was determined with 11 clinical tests. The elongation of the patellar tendon was assessed during graded maximal isometric knee extensor contractions using ultrasonography, and the mechanical properties of the patellar tendon were determined from corresponding load and tendon deformation data. The two groups were similar with respect to weight, height, tendon cross-sectional area and length, and were, furthermore, equally physically active. The knee joint ROM and lower extremity joint ROM score was significantly different between the groups (flexible: 136+/-7 degrees vs inflexible: 76+/-16 degrees , P<0.001 and flexible: -4.7+/-1.3 vs inflexible: 3.1+/-4.1, P<0.001). There was no difference between groups in maximal knee extensor force or the corresponding tendon deformation. The tendon stiffness (flexible: 3269+/-1591 vs inflexible: 3185+/-1457 N/mm), stress (flexible: 22.4+/-6.5 vs inflexible: 34.0+/-17.6 N/mm(2)), strain (flexible; 6.5+/-1.6 vs inflexible: 7.2+/-1.9%) and Young's modulus (flexible: 0.81+/-0.35 vs inflexible: 1.22+/-0.52 GPa) were not different between the two groups of subjects. These data suggest that differences in knee joint ROM cannot be explained by the mechanical properties of the patellar tendon.     

The effect of heat applied with stretch to increase range of motion: A systematic review

Application of heat to muscle is commonly advocated to enhance the efficacy of stretching. However, the effect of this combined therapy using different methods of heating, applied to different muscles, and after one or multiple treatments, is not known.To perform a systematic review to address the question: Does stretching augmented by heat application result in greater gains in range of motion (ROM) compared to stretch alone?The following databases were searched for original articles that evaluated our question: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, SPORTDiscus and PEDro databases. After title and abstract screening followed by full-text screening, the quality of included articles was assessed and their data was abstracted. Screening, data abstraction and quality assessment was performed and consensus was achieved by two reviewers. Range of motion (ROM) data were synthesized by meta-analyses for overall effect and subgroup analysis according to muscle group, method of heat application, single or multiple treatments, and reported tightness of muscle. Twelve studies were included and reported the effects of stretch with or without heat on ROM of 352 participants. Heat applications included ultrasound, shortwave diathermy and hot packs. Meta-analyses and subgroup analyses demonstrated greater increases in ROM after heat and stretch (H + S) than heat alone. Subgroup analysis of muscle groups and the method of heat application showed some trends, but no significant differences. Multiple treatments (more so than single treatments) showed consistent treatment effects of H + S versus stretch alone amongst subgroups. Muscles described as tight did not show a greater treatment effect in response to H + S compared to muscles not reported as tight.Heating provides an added benefit on stretch related gains of ROM in healthy people.     

Bilateral consecutive rupture of the quadriceps tendon in a man with BstUI polymorphism of the COL5A1 gene

A genetic component has been implicated in tendinopathies involving tendon rupture. Type V collagen, a quantitatively minor fibrillar collagen which forms heterotypic fibrils with type I collagen, plays a role in the regulation of the size and configuration of fibrils of the much more abundant component type I collagen. To date, no data on the genetic component of bilateral rupture of the quadriceps tendon have been reported. We describe the presence of BstUI polymorphism of the COL5A1 gene in a man with bilateral rupture of the quadriceps tendon. The COL5A1 (the variant rs12722, BstUI RFLP) can be a candidate gene associated with the development of bilateral quadriceps tendon rupture.     

Association between an indel polymorphism in the 3′UTR of COL1A2 and the risk of sudden cardiac death in Chinese populations

Sudden cardiac death (SCD) describes the unexpected natural death from a cardiac cause within a short time period. Compelling evidence suggests the involvement of host genetic factors in SCD etiology. Identification of genetic variations predisposed to SCD enables genetic testing that may contribute to SCD diagnosis and risk stratification. Previous studies have suggested that dysregulation of pro-alpha2 chain of type I collagen, encoded by collagen type I alpha 2 chain (COL1A2) gene, was involved in cardiac disorders such as myocardial infarction, hypertrophic cardiomyopathy and atherosclerosis. By using a candidate-gene-based approach, we evaluated the association of a 7-base pair (7-bp) indel polymorphism (rs3917) in the 3′UTR of COL1A2 with the risk of SCD in a Chinese population (79 SCD cases and 328 controls). Logistic regression analysis showed that the deletion allele of rs3917 significantly increased the risk of SCD [odds ratio (OR) = 1.82; 95% confidence interval (CI) = 1.08–3.06; P = 0.0159]. Further genotype-phenotype association analysis revealed that the deletion allele was markedly correlated with lower expression of COL1A2 in human myocardium tissues. The luciferase activity analysis in an in vitro reporter gene system suggested that rs3917 could regulate COL1A2 expression through interrupting the binding of miR-296-3p with COL1A2 in an allele-dependent manner, which in turn confer SCD risk. Our data provided initial evidence that rs3917 was highly relevant to SCD susceptibility, and this indel may become a potential marker for molecular diagnosis and genetic counseling of SCD. The replication of our studies and further functional studies are needed to validate our findings.     

Perception of whole-body motion during balance perturbations is impaired in Parkinson's disease and is associated with balance impairment

BackgroundIn addition to motor deficits, Parkinson's disease (PD) may cause perceptual impairments. The role of perceptual impairments in sensorimotor function is unclear, and has typically been studied in single-joint motions.Research questionWe hypothesized that perception of whole-body motion is impaired in PD and contributes to balance impairments. We tested (1) whether directional acuity to whole body perturbations during standing was worse in people with PD compared to neurotypical older adults (NOA), and (2) whether balance ability, as assessed by the MiniBESTest, was associated with poor directional acuity in either group.MethodsParticipants were exposed to pairs of support-surface translation perturbations in a two-alternative forced choice testing paradigm developed previously in a young healthy population. The first perturbation of each pair that was to be judged by participants was directly backward, and the second perturbation deviated from the left or right from the backward direction by 1°–44°. Participants reported whether the perturbations in each pair were in the “same” or “different” direction. Judgements from 24 to 67 perturbation pairs were used to calculate directional acuity thresholds corresponding to “just-noticeable differences” in perturbation direction. Linear mixed models determined associations between directional thresholds and clinical variables including MDS-UPDRS-III score, age, and MiniBESTest score.Results20 PD (64 ± 7 y, 12 male, ≥12 h since last intake of antiparkinsonian medications) and 12 NOA (64 ± 8, 6 male) were assessed. Directional thresholds were higher (worse) among PD participants (17.6 ± 5.9° vs. 12.8 ± 3.3°, P < 0.01). Linear mixed models further showed that higher thresholds were associated with MDS-UPDRS-III score (P < 0.01), and were associated with poorer balance ability among PD participants (P < 0.01), but not among NOA participants (P = 0.40).SignificancePerception of whole-body motion is impaired in PD and may contribute to impaired balance and falls.     

TPH1 A218 allele is associated with suicidal behavior in Turkish population

BackgroundSerotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. The first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is encoded by TPH1 and THP2 genes. Genetic association studies have revealed contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism on suicidal behavior in different populations.Material and methodIn this study, we investigated A218C polymorphism in 109 suicide attempters and 98 healthy controls. Socio-demographic characteristics of participants were obtained through questionnaire. DNA was extracted from peripheral blood and genotyping was performed by Real Time PCR. Fisher’s exact test was used to evaluate the significance of the difference among the independent variables. Hardy-Weinberg equilibrium was tested using Pearson’s goodness-of-fit chi-squared test.ResultsThe frequency of A allele was significantly higher in suicide attempters than controls (46.33% vs. 35.71%, p = 0.0357). However, there were no differences in genotype frequencies of this locus between participants having attempted suicide and controls (p > 0.05). Among males, frequencies of CC genotype and C allele were found to be significantly higher in controls (p = 0.0125, p = 0.0298). With regard to the female subjects and female controls, no significant association was detected between suicidal behavior and genotype/allele frequencies (p > 0.05).ConclusionOur results provide evidence that A allele of TPH1 A218C polymorphism may be associated with suicidal behavior in Turkish population.     

Mice with a deletion in the first intron of the Col1a1 gene develop dissection and rupture of aorta in the absence of aneurysms: high-resolution magnetic resonance imaging, at 4.7 T, of the aorta and cerebral arteries.

Deletion of the majority of the first intron of the Col1a1 gene in mice leads to decreased type I collagen synthesis and content in the aortic wall. In 54% of cases, mice homozygous for the Col1a1 mutation die of thoracic hemorrhage by the age of 18 months. It is unknown whether the fatal bleeding results from an acute dissection of the aortic wall or a gradually developing dilatation of the medial layer prior to rupture. We optimized high-resolution MRI methods using a 4.7 T MR scanner to obtain in vivo images of the entire mouse aorta. The MR images were acquired in three imaging planes using gradient echo, spin echo, and spin echo with inversion recovery pulse sequences with a maximum in-plane resolution of 68 x 68 microm and acquisition times less than 10 min. In five Col1a1 mutated mice aged 16 months, the MR images showed no signs of aneurysmal dilatation, wall defects, or former dissection, suggesting that the mechanism for aortic rupture is an acute dissection of the aortic medial layer. Cerebral arteries were imaged using a three-dimensional time of fight pulse sequence. The resolution of 73 x 73 x 94 microm showed normal cerebral arteries. Histology showed a 22% thinner cerebral artery wall in Col1a1 mutated mice.     

血管紧张素原基因M235T和血管紧张素受体1基因A1166C多态性与飞行员原发性高血压的相关性

目的探讨血管紧张素原(AGT)基因M235T和血管紧张素受体1(AT1R)基因A1166C多态性与飞行员原发性高血压的相关性,为飞行员原发性高血压的预防提供依据。方法用聚合酶链反应(PCR)和限制性酶切检测48例飞行员原发性高血压患者和50例飞行员健康对照者的AGT M235T和AT1R A1166C多态性。结果飞行员高血压组AGT M235基因型和等位基因频率与健康对照组有明显差异,而AT1R A1166C两组间差异无统计学意义。结论 AGT M235T基因多态性与飞行员原发性高血压相关。     

A history of concussions is associated with symptoms of common mental disorders in former male professional athletes across a range of sports

Objective: Recent reports suggest that exposure to repetitive concussions in sports is associated with an increased risk of symptoms of distress, anxiety and depression, sleep disturbance or substance abuse/dependence (typically referred as symptoms of common mental disorders[CMD]) and of later development of neurodegenerative disease, in particular chronic traumatic encephalopathy (CTE). The primary aim of this study was to explore the relationship between sports career-related concussions and the subsequent occurrence of symptoms of CMD among former male professional athletes retired from football (soccer), ice hockey and rugby (union).

Methods: Cross-sectional analyses were performed on baseline electronic questionnaires from three prospective cohort studies among former male professional athletes retired from football (soccer), ice hockey and rugby (union). The number of confirmed concussions was examined through a single question, while symptoms of distress, anxiety and depression, sleep disturbance and adverse alcohol use were assessed using validated questionnaires.

Results: From 1,957 former professional athletes contacted, a total of 576 (29%) completed the questionnaire. Of these, 23% had not incurred a concussion during their career, 34% had two or three, 18% four or five, and 11% six or more concussions. The number of sports career-related concussions was a predictor for all outcome measures (β = 0.072–0.109; P ≤ 0.040). Specifically, former professional athletes who reported a history of four or five concussions were approximately 1.5 times more likely to report symptoms of CMD, rising to a two- to five-fold increase in those reporting a history of six or more sports career-related concussions.

Conclusions: These data demonstrate an association between exposure to sports concussion and subsequent risk of symptoms of CMD in former professional athletes across a range of contact sports. Further work to explore the association between sports concussion and symptoms of CMD is required; in the meanwhile, strategies for effective risk reduction and improved management appear indicated.     

MMP-2C-735T基因多态性与高血压伴颈动脉粥样硬化的关系

 目的 研究基质金属蛋白酶-2(matrix metalloproteinase 2,MMP-2)C-735T与原发性高血压(essential hypertension,EH)伴颈动脉粥样硬化(carotid a山erosclerosis,CAS)的关系.方法 采用病例-对照研究,应用聚合酶链反应-限制性片断长度多态性(polymerase chain reaction-restiction fragment length polymorphism,PCR-RELP)技术测定MMP-2 C-735T基因多态性.结果 AS组的T等位基因频率明显高于NS组(X2=7.144,P=o.008).结论 MMP-2基因C-735T多态性可能与汉族EH患者伴CAS有关,T等位基因可能增加EH患者伴发CAS的风险.