This SNP, in the ACTN3 gene, encodes a premature stop codon in a muscle protein called alpha-actinin-3. The polymorphism alters position 577 of the alpha-actinin-3 protein.
In the (C;C) genotype is often called RR. The truncated (T;T) is often called XX.
[PMID 18043716] (T;T) is under-represented in elite strength athletes, consistent with previous reports indicating that alpha-actinin-3 deficiency appears to impair muscle performance.
The most common nucleotide at this position, (C), encodes an arginine (amino acid code R), the alternative T allele encodes a stop codon (X). Hence, the SNP is referred to as R577X, with homozygotes being either RR or XX and heterozygotes being RX. XX individuals completely lack the expression of alpha-actinin-3.
An earlier report studying a relatively small number of Australian elite (i.e. ~Olympic) athletes found that, at least in females, the R allele (ie rs1815739(C)) is associated with sprinters, while the X allele (rs1815739(T)) is associated with endurance athletes. No female or Olympic-level sprinters were XX homozygotes (rs1815739(T;T)). The association tended the same way but was statistically weaker in males. [PMID 12879365]
There have been several subsequent studies, but few with large sample sizes and thus few with much statistical power. An example of a typical study: no increase in endurance ability was associated with the X allele in elite male cyclists. [PMID 16612741]
An extensive blog post from one of the original authors of this research.
|Disease||ACTININ, Actn3 deficiency, Sprinting performance|
|CLNDBN||ACTININ, ALPHA-3 POLYMORPHISM, Actn3 deficiency, Sprinting performance|
|CLNSRC||OMIM Allelic Variant|
|CLNACC||RCV000019974.1, RCV000019975.1, RCV000019976.1|
[PMID 18852891] Distribution and effects of nonsense polymorphisms in human genes.
[PMID 19237423] Is there an optimum endurance polygenic profile?
[PMID 19544227] ACTN3 R577X polymorphism and Israeli top-level athletes.
[PMID 20005538] Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?
[PMID 20561285] ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.
[PMID 20585627] Web-based, participant-driven studies yield novel genetic associations for common traits.
[PMID 20845221] ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.
[PMID 20936592] Association between the ACTN3 R577X polymorphism and female endurance athletes in China.
[PMID 21407828] Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.
[PMID 21542061] ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies.
[PMID 22224919] ACTN3 R577X polymorphism and performance phenotypes in young Chinese male soldiers.
|qualified_impact||Insufficiently evaluated not reviewed|