A common nonsense mutation results in α-actinin-3 deficiency in the general population

North, Klaus; Yang, Nan; Wattanasirichaigoon, Duangrurdee; Mills, Michelle A.; Easteal, Simon; Beggs, Alan H.

doi:10.1038/7675

Cited by 378 publications

(322 citation statements)

References 11 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…This protein is almost exclusively expressed in fast-twitch (type II) skeletal muscle fibres (Mills et al 2001); thus, compared to the I type, α-actinin-3 may confer type II fibres with a higher capacity for the absorption/transmission of force at the Z line during rapid contractions (Squire 1997). The R577X polymorphism (rs1815739) of the gene (ACTN3) encoding α-actinin-3, which results from a C-to-T transition at position 1,747 in exon 16 that substitutes an arginine residue at codon 577 for a premature stop codon (North et al 1999), may be associated with muscle phenotypes, particularly with the ability to produce powerful muscle contractions (MacArthur et al 2007). The α-actinin-3-deficient XX genotype (with a frequency of~18% among European Caucasians) is believed to preclude top-level athletic performance in 'pure' power and sprint sports (e.g.…”

Section: Genotype-phenotype Association Studiesmentioning

confidence: 99%

Genes and the ageing muscle: a review on genetic association studies

Garatachea

Lucía

2011

AGE

View full text Add to dashboard Cite

Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensinconverting enzyme (ACE) gene I/D, α-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions.

show abstract

Section: Genotype-phenotype Association Studiesmentioning

confidence: 99%

Genes and the ageing muscle: a review on genetic association studies

Garatachea

Lucía

2011

AGE

View full text Add to dashboard Cite

show abstract

“…Среди нуклеотидных замен гена ACTN3 наиболее известна замена C → T в локусе rs1815739, которая приводит к терминации синтеза белка в аминокислотной позиции 577 экзона 16, что происходит вследствие замены аргинина на терминирующий кодон (замены R577X) [2]. Такого рода замена приводит к дефициту α-актинина-3 в быстросокращающихся мышеч-ных волокнах, что, в свою очередь, может стать причиной снижения ско-ростно-силовых показателей физической работоспособности человека [3].…”

Section: Introductionunclassified

R577X polymorphism of alpha-actinin-3 in human populations of North-Eastern Asia

Malyarchuk

Аркадьевич²,

Derenko

et al. 2017

Ecological genetics

View full text Add to dashboard Cite

Background. In polymorphism rs1815739, a C → T transition converts arginine to a premature stop-codon at residue 577 of the alpha-actinin-3 (ACTN3) protein (R577X polymorphism). This polymorphism may affect muscle performance, and the derived 577X allele has been found to be under-represented in sprint/power athletes. In addition, loss of alpha-actinin-3 results in a shift in muscle metabolism toward the more efficient aerobic pathway, thus pointing that this polymorphism may have been involved in enhancing the capability for hunting and for cold adaptation. Here, we study rs1815739 polymorphism in native populations (Chukchi, Koryaks and Evens) and newcomers (Russians) of North-Eastern Asia. Materials and methods. Genomic DNA was isolated from peripheral blood. ACTN3 genotypes for rs1815739 locus were established by enzymatic digestion of amplicons with DdeI. Heterozygotes TT were confirmed by DNA sequencing. In addition, data on exome variation in Siberian populations were analyzed. Results. Lowered frequencies (less than 40%) of “mutant” allele rs1815739-T were found in studied populations of North-Eastern Asia. Analysis of exome data has shown that haplotype comprising the rs1815739-T allele reaches the highest frequencies in populations of Southern and Central Siberia, while it is rather rare in the north-east of Siberia. Conclusion. The results obtained contradict the hypothesis that the rs1815739 polymorphism may have been involved in cold adaptation of North-East Siberians.

show abstract

“…In humans, there are two genes encoding skeletal-muscle α-actinins: ACTN2, which is expressed in all fi bers, and ACTN3, which expression is restricted to fast (type 2) myofi bers responsible for generating force at high velocity. It is been demonstrated that α-actinin-3 defi ciency is common in the general population due to homozygocity for a premature stop codon (50). In fact, the skeletal-muscle actin-binding protein α-actinin-3 is absent in approximately 20 % of healthy individuals (with ethical variations) because of homozygocity for a common stop-codon polymorphism in the ACTN3 gene, R577X.…”

Section: Other Applications Of the Genetic Predisposition Testingmentioning

confidence: 99%