ACTN3

(Alpha-actinin skeletal muscle isoform 3) (F-actin cross-linking protein)

Publications

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Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age.

PubMed

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Studies of the gene and miRNA expression profiles associated with the postnatal late growth, development, and aging of skeletal muscle are lacking in sika deer. To understand the molecular mechanisms of the growth and development of sika deer skeletal muscle, we used de novo RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) analyses to determine the differentially expressed (DE) unigenes and miRNAs from skeletal muscle tissues at 1, 3, 5, and 10 years in sika deer. A total of 51,716 unigenes, 171 known miRNAs, and 60 novel miRNAs were identified based on four mRNA and small RNA libraries. A total of 2,044 unigenes and 11 miRNAs were differentially expressed between adolescence and juvenile sika deer, 1,946 unigenes and 4 miRNAs were differentially expressed between adult and adolescent sika deer, and 2,209 unigenes and 1 miRNAs were differentially expressed between aged and adult sika deer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that DE unigenes and miRNA were mainly related to energy and substance metabolism, processes that are closely associate with the growth, development, and aging of skeletal muscle. We also constructed mRNA-mRNA and miRNA-mRNA interaction networks related to the growth, development, and aging of skeletal muscle. The results show that mRNA (Myh1, Myh2, Myh7, ACTN3, etc.) and miRNAs (miR-133a, miR-133c, miR-192, miR-151-3p, etc.) may play important roles in muscle growth and development, and mRNA (WWP1, DEK, UCP3, FUS, etc.) and miRNAs (miR-17-5p, miR-378b, miR-199a-5p, miR-7, etc.) may have key roles in muscle aging. In this study, we determined the dynamic miRNA and unigenes transcriptome in muscle tissue for the first time in sika deer. The age-dependent miRNAs and unigenes identified will offer insights into the molecular mechanism underlying muscle development, growth, and maintenance and will also provide valuable information for sika deer genetic breeding.

MeSH Terms

• Aging
• Animals
• Deer
• Gene Expression Profiling
• Gene Expression Regulation, Developmental
• High-Throughput Nucleotide Sequencing
• MicroRNAs
• Muscle Development
• Muscle, Skeletal
• RNA, Messenger
• Transcriptome

Keywords

• age-dependent
• mRNA
• microRNA
• sika deer
• skeletal muscles

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The Role of Genetic Profile in Functional Performance Adaptations to Exercise Training or Physical Activity: A Systematic Review of the Literature.

PubMed

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[i] :[/i] Variations in genotype may contribute to heterogeneity in functional adaptations to exercise. [i] :[/i] A systematic search of eight databases was conducted, and 9,696 citations were screened. [i] :[/i] Eight citations from seven studies measuring 10 single-nucleotide polymorphisms and nine different functional performance test outcomes were included in the review. There was one observational study of physical activity and six experimental studies of aerobic or resistance training. The ACE (D) allele, ACTN3 (RR) genotype, UCP2 (GG) genotype, IL-6-174 (GG) genotype, TNF-α-308 (GG) genotype, and IL-10-1082 (GG) genotype all predicted significantly superior adaptations in at least one functional outcome in older men and women after prescribed exercise or in those with higher levels of physical activity. [i] :[/i] There is a small amount of evidence that older adults may have better functional outcomes after exercise/physical activity if they have specific alleles related to musculoskeletal function or inflammation. However, more robust trials are needed.

MeSH Terms

• Activities of Daily Living
• Aged
• Aged, 80 and over
• Aging
• Exercise
• Genetic Profile
• Humans
• Physical Fitness

Keywords

• genotype
• mobility
• performance-based testing
• polymorphism

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Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.

PubMed

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A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.

MeSH Terms

• Actinin
• Africa
• Aging
• Athletic Performance
• Genotype
• Human Migration
• Humans
• Muscular Diseases
• Polymorphism, Single Nucleotide
• Selection, Genetic

Keywords

• ACTN3
• ageing
• athletic performance
• genetic variant
• muscle disease
• α-actinin-3

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ACTN3 genotype and physical function and frailty in an elderly Chinese population: the Rugao Longevity and Ageing Study.

PubMed

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To examine the associations of the actinin alpha 3 gene (ACTN3) R577X polymorphism with physical performance and frailty in an older Chinese population. Data from 1,463 individuals (57.8% female) aged 70-87 years from the Rugao Longevity and Ageing Study were used. The associations between R577X and timed 5-m walk, grip strength, timed Up and Go test, and frailty index (FI) based on deficits of 23 laboratory tests (FI-Lab) were examined. Analysis of variance and linear regression models were used to evaluate the genetic effects of ACTN3 R577X on physical performance and FI-Lab. The XX and RX genotypes of the ACTN3 R557X polymorphism accounted for 17.1 and 46.9%, respectively. Multivariate regression analysis revealed that in men aged 70-79 years, the ACTN3 577X allele was significantly associated with physical performance (5-m walk time, regression coefficient (β) = 0.258, P = 0.006; grip strength, β = -1.062, P = 0.012; Up and Go test time β = 0.368, P = 0.019). In women aged 70-79 years, a significant association between the ACTN3 577X allele and the FI-Lab score was observed, with a regression coefficient of β = 0.019 (P = 0.003). These findings suggest an age- and gender-specific X-additive model of R577X for 5-m walk time, grip strength, Up and Go Test time, and FI-Lab score. The ACTN3 577X allele is associated with an age- and sex-specific decrease in physical performance and an increase in frailty in an older population.

MeSH Terms

• Actinin
• Age Factors
• Aged
• Aged, 80 and over
• Asian Continental Ancestry Group
• China
• Female
• Frailty
• Gene Frequency
• Genetic Predisposition to Disease
• Geriatric Assessment
• Hand Strength
• Humans
• Longevity
• Male
• Phenotype
• Polymorphism, Genetic
• Real-Time Polymerase Chain Reaction
• Risk Assessment
• Risk Factors
• Sex Factors
• Walk Test

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Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians.

PubMed

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Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the 'highly oxidative/efficient' rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a "healthy" metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved.

MeSH Terms

• Actinin
• Alleles
• Asian Continental Ancestry Group
• Female
• Gene Frequency
• Genetic Association Studies
• Genotype
• Humans
• Japan
• Longevity
• Male
• Myostatin
• Polymorphism, Genetic
• Population Surveillance

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Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

PubMed

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Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage.

MeSH Terms

• Aging
• Athletic Performance
• Cumulative Trauma Disorders
• Genetic Predisposition to Disease
• Genetic Variation
• Humans
• Models, Genetic
• Muscle, Skeletal
• Muscular Diseases
• Polymorphism, Single Nucleotide

Keywords

• Creatine kinase
• Delayed onset muscle soreness
• Elderly
• Exercise-induced muscle damage
• Single nucleotide polymorphism

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The ACTN3 R577X genotype is associated with muscle function in a Japanese population.

PubMed

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Homozygosity for the common nonsense polymorphism R577X in the α-actinin-3 gene (ACTN3) causes complete α-actinin-3 deficiency in fast-twitch skeletal muscle fibers. This study investigated whether the ACTN3 R577X polymorphism affects fitness status using a battery of tests in a large Japanese cohort. In the present study, 1227 subjects (age: 25-85 years) were genotyped for the ACTN3 R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied Biosystems). All subjects were divided into 2 groups based on their age (<55 years and ≥55 years). All subjects completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their fitness status (including grip strength test, chair stand test, and 8-foot walking test). A significant association between the ACTN3 R577X genotype and chair stand test performance was observed in the group of men ≥55 using ANCOVA adjusted for age and exercise habits (p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of the variability in the results of the chair stand test among men in the ≥55 age group. Moreover, for the ≥55 age group, performance in the chair stand test was lower among those with the XX genotype than among those with the RR genotype (p = 0.024) or RX genotype (p = 0.005), unlike results for the <55 age group. No significant difference was noted for hand grip strength or 8-foot walking time. Thus, our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population.

MeSH Terms

• Actinin
• Adult
• Aged
• Aged, 80 and over
• Asian Continental Ancestry Group
• Body Mass Index
• Codon, Nonsense
• Cohort Studies
• Exercise
• Female
• Gene Deletion
• Hand Strength
• Health Behavior
• Homozygote
• Humans
• Male
• Middle Aged
• Muscle Fibers, Fast-Twitch
• Polymorphism, Genetic
• Surveys and Questionnaires

Keywords

• aging
• batterie de tests
• fonction musculaire
• force musculaire
• muscle function
• muscle strength
• polymorphism
• polymorphisme
• test battery
• vieillissement
• α-actinin-3
• α-actinine-3

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1000 Norms Project: protocol of a cross-sectional study cataloging human variation.

PubMed

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Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or 'normal' values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. In 2012 the 1000 Norms Project Consortium defined the concept of 'normal', established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype ('gene for speed'). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures.

MeSH Terms

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Cross-Sectional Studies
• Exercise
• Female
• Health Status
• Humans
• Male
• Middle Aged
• Muscle Strength
• Musculoskeletal Pain
• Psychometrics
• Quality of Life
• Range of Motion, Articular
• Reference Values
• Self Efficacy
• Surveys and Questionnaires
• Work Capacity Evaluation
• Young Adult

Keywords

• Healthy
• Lifespan
• Physical assessment
• Reference values

{{medline-entry |title=ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22855367 |abstract=Genetic variation of the human ACE I/D and ACTN3 R577X polymorphisms subsequent to 12 weeks of high-speed power training on maximal strength (1RM) of the arm and leg muscles, muscle power performance (counter-movement jump), and functional capacity (sit-to-stand test) was examined in older Caucasian women [n = 139; mean age 65.5 (8.2) years; 67.0 (10.0) kg and 1.57 (0.06) m]. Chelex 100 was used for DNA extraction, and genotype was determined by PCR-RFLP methods. Muscular strength, power, and functional testing were conducted at baseline (T1) and after 12 weeks (T2) of high-speed power training. At baseline, the ACE I/D and ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian women. After the 12-week high-speed training program, subjects significantly increased their muscular and functional capacity performance (p < 0.05). For both polymorphisms, significant genotype-training interaction (p < 0.05) was found in all muscular performance indices, except for 1RM leg extension in the ACE I/D (p = 0.187). Analyses of the combined effects between genotypes showed significant differences in all parameters (p < 0.05) in response to high-speed power training between the power (ACTN3 RR RX