Rs1815739

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.

(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.

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.

An extensive blog post from one of the original authors of this research.

This is one of the SNPs reported by NutraHacker.

Distribution and effects of nonsense polymorphisms in human genes.

Is there an optimum endurance polygenic profile?

ACTN3 R577X polymorphism and Israeli top-level athletes.

Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?

ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

Web-based, participant-driven studies yield novel genetic associations for common traits.

ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.

Association between the ACTN3 R577X polymorphism and female endurance athletes in China.

Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies.

ACTN3 R577X polymorphism and performance phenotypes in young Chinese male soldiers.