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 publications the (C;C) genotype is often called RR, whereas the (T;T) genotype is often called XX. According to (T;T) is under-represented in elite strength athletes, consistent with previous reports indicating that alpha-actinin-3 deficiency appears to impair muscle performance. However in 2016 failed to replicate casting some doubt. 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. One of the earliest 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. One paper has found that the X allele profile of centenarians resembles that of world-class elite endurance athletes. 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.

C;C

This genotype indicates better performing muscles, particularly for sprinting and power sports. Fast-twitch muscle fibers are able to produce alpha-actinin-3. Professional sprinters usually have this, although it is less common for endurance athletes.

C;T

Normal for white people. One working and one defective copy of the gene for alpha-actinin-3 in fast-twitch muscle fibres. This genotype may indicate somewhat impaired muscles, however many sprinters and some endurance athletes have this.

T;T

Early reports such as suggested this is under-represented in elite strength and sprint athletes, consistent with previous reports of impaired muscle performance. However this is more common in endurance athletes. This SNP makes fast-twitch muscle fibers completely unable to produce alpha-actinin-3. In 2016 a larger attempt at replication failed to find any signficant result