ACTN3 (R577X) genotype is associated with fiber type distribution

Abstract

is a Z-disc structural protein found only in type II muscle fibers. The X allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and ␣-actinin-3 deficiency in XX homozygotes. Associations between the R577X polymorphism and the muscle-power performance of elite athletes have been described earlier. About 45% of the fiber type proportions are determined by genetic factors. The ACTN3 variant could be one of the contributing genes in the heritability of fiber type distribution through its interaction with calcineurin. The aim of this study was to quantify the association between the polymorphism and muscle fiber type distribution and fast-velocity knee extension strength. Ninety healthy young men (18 -29 y) were genotyped for ACTN3 R577X. Knee extensor strength was measured isometrically (45°) and at different dynamic velocities (100 -300°/s) on a programmable dynamometer. Twenty-two XX and twenty-two RR subjects underwent a biopsy of the right vastus lateralis muscle. Fiber type composition was determined by immunohistochemistry. Homozygotes for the R allele show significantly higher relative dynamic quadriceps torques at 300°/s, compared with XX carriers (P Ͻ 0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers were greater in the RR than the XX genotype group (P Ͻ 0.05), and ␣-actinin-3 protein content is systematically higher in type IIx compared with type IIa fibers (staining intensity ratio IIx to IIa ϭ 1.17). This study shows that the mechanism, by which the ACTN3 polymorphism has its effect on muscle power, might rely on a control function of fiber type proportions.

Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene

“…We genotyped this SNP in a limited sample (N¼16) from an independent study conducted in our research center from which muscle tissue biopsies were available. 24 Relative expression levels were 0.93 ± 0.18 and 0.95 ± 0.25 for AA homozygotes and G-allele carriers, respectively, and did not differ significantly (P¼0.80).…”

“…24 A detailed description of the mRNA extraction and real-time PCR chr12q12-14 fine mapping: ACVR1B and muscle strength A Windelinckx et al protocol for ACVR1B mRNA expression is available in Supplementary file 1 and elsewhere. 25 …”

Genetic aspects of skeletal muscle strength and mass with relevance to sarcopenia

“…76,78,80,82,106 Of those studies, only Walsh et al 78 and Zempo et al 106 found evidence of an association between muscle size and the ACTN3 null X allele, indicating at best a minor role for this polymorphism in explaining interindividual variability in this trait.…”

ACTN 3 e desempenho esportivo: um gene candidato ao sucesso em provas de curta e longa duração.<br>DOI:10.5007/1980-0037.2011v13n6p477

“…Na linha Z, as α-actininas são componentes primordiais, pois se ligam aos filamentos de actina de sarcômeros adjacentes, cumprindo a função de ancoragem dos filamentos finos e formando uma estrutura estabilizadora do tecido muscular durante a contração 20 . Adicionalmente à sua função na organização estrutural do sarcômero, estudos recentes sugerem que as α-actininas sarcoméricas também atuam na regulação do processo contrátil, na regulação do metabolismo energético e possivelmente, na determinação do tipo de fibra muscular 12,19,21 . Tal diversidade de função tem sido atribuída à grande capacidade que as α-actininas, em especial a isoforma -3, têm de se ligar a outras proteínas e outros elementos regulatórios intracelulares 22 .…”

“…Vale salientar que as calsarcinas localizam-se na linha Z e apresentam-se ligadas à calcineurina, uma proteína Ca2+ CaM-dependente, um importante sinalizador muscular que exerce relevante papel na determinação do tipo de fibra 26 e na hipertrofia 27 . Devido a essa interação com a calcineurina, Vincent et al 21 investigaram a relação entre a porcentagem dos tipos de fibra muscular e a ausência de α-actinina-3. Os resultados mostraram que indivíduos com o genótipo RR (expressão da forma funcional da α-actinina-3) apresentaram maior porcentagem de fibras tipo IIx (14±2%) em relação a indivíduos XX (expressão da forma truncada) (9±1%).…”