User:Dylanjjenkins/sandbox

The X homozygous genotype is caused by a C to T transition in exon 16 of the ACTN3 gene, which causes a transformation of an arginine base (R) to a premature stop codon (X) resulting in the rs1815739 mutation causing no production of the alpha-actinin 3 protein in muscle fibers. This phenomenon was confirmed through a study of mice. In mice with X homozygosity, Lactate Dehydrogenase (LDH), used in fast muscle fiber pyruvate metabolism, was 16% lower than usual. Meanwhile, the mice with an XX mutation had 22% higher citrate synthase presence, which catalyzes the slower but more efficient pyruvate metabolism process present in slow twitch muscle fibers. The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch fibers. Lacking the proteins necessary for fast twitch muscle fibers to optimally function, causes the body to shift towards heavier use of the slow twitch muscle fibers which is evident by the 22% higher citrate synthase presence in mice with the 577XX polymorphism.

Despite causing decreased muscle size, strength and power, the deficiency is present in 10-50% of people based on ethnicity. Asians have the highest frequency of the 577X allele at nearly 50%, while African Bantu has the lowest 577X frequency of the ethnic groups studied at only about 10%.

ACTN3 in Athletes
The R allele frequency of the ACTN3 gene has been shown to be substantially greater in sprint and powerlifting athletes as compared to the general public because of the short bursts of power required for these sports. There has been some evidence suggesting there may be some connection between X homozygosity and endurance athlete performance because the muscles are using a more efficient form of pyruvate metabolism benefitting events requiring endurance. However, other studies have shown little correlation between the homozygous X genotype and endurance athlete performance.

There have also been some links between the ACTN3 gene in relation to both injuries in sports and recovery from workouts. According to a collection of literature, most research performed have shown the XX genotype is associated with higher levels of muscle damage resulting in a longer time required for recovery. There has also been some evidence to suggest the R allele has some sort of protection against injury in athletes. One such study examined injury occurrence in professional soccer players. The results showed players with the XX genotype were 2.66 times more likely to suffer a minor injury and 2.13 times more likely to suffer a severe injury as compared to their RR counterparts, while RX genotype athletes had similar likelihood to suffer a minor injury and 1.63 times higher odds of suffering a severe injury as compared to athletes with an RR genotype. The findings in the studies contained in the review of literature suggest an association between the ACTN3 R577X polymorphism in exercise recovery and injury risk in addition to its already widely accepted role in sprint and powerlifting performance at an elite level.

Alleles
An allele (rs1815739; R577X) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin 3 in a significant proportion of the population. The X homozygous genotype is caused by a C to T transition in exon 16 of the ACTN3 gene, which causes a transformation of an arginine base (R) to a premature stop codon (X) resulting in the rs1815739 mutation causing no production of the alpha-actinin 3 protein in muscle fibers. The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers.

It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.

Athletes
There is an association between the ACTN3 R577X polymorphism in sprint and powerlifting performance at an elite level, and appears to be an association with exercise recovery and lower injury risk. It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.