ACTN3 fast/slow muscle twitch
Muscle fiber type
Genetic polymorphism in the ACTN3 gene is of the most studied in sport genetics. Tens of thousands of athletes and controls were tested for this variant. Along with the HIF1A gene, these genes are major determinants for muscle fiber type proportion. One genetic set-up is optimal for fast and powerful muscle contraction needed for top-class sprint and power performance. Another set-up is resistant to fatigue and optimal for endurance performance.
A muscle contains a mixture of fast and slow fiber types.
Type I muscle fibers are slow twitch fibers that use energy efficiently and can contract and expand for extended periods of action. It supports aerobic activity as oxygen supply is sufficient to produce energy by respiration.
Fast twitch fibers on the other hand are able to contract more rapidly. It uses anaerobic metabolism to create energy when oxygen levels are low. These fibers provide high work rate, for short periods of action.
Endurance athletes show a high proportion of Type I fibers, while muscles of power athletes predominantly consist more type II fibers. An average untrained individual have an equal proportion for each type.
Muscle fiber composition is highly heritable, determining 40-50% of this trait. genetic variants involved in the regulation of muscle fiber characteristics may predispose differentiation of young, precursor muscle cells to be predominantly fast or slow, tipping his potential capabilities in endurance and power sports.
There are two genes highly associated with muscle fiber contraction ability and power performance. The most studied gene in sports genetics is the ACTN3 gene. Tens of thousands of athletes and controls were tested for its variant, providing evidence for the main role it plays in determining muscle fiber abilities. The second gene, HIF1A, is the second most associated genetic factor of fiber content in large and recent meta-analysis studies.
Gene: ACTININ, ALPHA-3 (ACTN3)
Genomic coordinates (GRCh38): 11:66,546,394-66,563,328
Genetic polymorphism in the ACTN3 gene is of the most studied in sport genetics. Majority of studies conclude that one ACTN3 set-up is optimal for fast muscle function needed for top-class sprint and power performance, while the other set-up is optimal for endurance performance.
ACTN3 encodes for the sarcomeric protein α-actinin-3 in muscle fibers. The expression of α-actinin-3 protein is almost exclusively restricted to fast, glycolytic, type 2 fibers, which are responsible for producing explosive powerful contraction.
Homozygosity for the common, null variant (XX genotype) results in complete deficiency of the α-actinin-3 protein. XX homozygotes carry no functional ACTN3 and survive due to functional redundancy between ACTN3 and ACTN2. However, that redundancy is incomplete since XX homozygotes are significantly less likely to become elite sprinters.
The ACTN3 XX frequency is very low among elite sprint/power athletes (i.e., sprinters, jumpers, and throwers). No Olympic-level sprinter has yet been identified with the 577XX genotype.
The XX genotype have less ‘fast’ glycolytic type II muscle fibers and more slower muscle fibers of types I and IIA. It is interesting to add that lower levels of testosterone were found in XX homozygotes.
A higher-then-expected frequency of the ACTN3 RR genotype is found in elite sprint/power athletes. On the other hand, XX genotype muscles exhibit 33% more endurance and increased activity of mitochondria.
Taken together, this evidence suggest that the XX genotype is detrimental, and RR genotype is optimal for fast muscle function needed for top-class sprint and power performance. In contrast, the XX genotype is beneficial for endurance athletes.
Gene: HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; (HIF1A)
Genomic coordinates (GRCh38): 14:61,695,400-61,748,258
The HIF1A gene controls the expression of several genes encoding for glycolytic enzymes. Epidemiological studies have found that a HIF1A variant is the second best predictor for muscle fiber type composition, after ACTN3.
Among Olympic speed skaters, carriers of the variant allele form had an increased proportion of fast-twitch muscle fibers in the vastus lateralis thigh muscle. Other studies found that carriers of the variant had a significantly higher percentage of type IIX muscle fibers. These fast-twitch glycolytic fibers are used predominantly in high explosive events, such as the 100-m sprint.
Another recent meta-analysis study has found that the frequency of the HIF1A variant was significantly higher in weight lifters than in controls (17.9% vs. 8.5%) and increased with their levels of achievement (subelite 14.7%, elite 18.8%, highly elite 25.0% prevalence). These results were replicated in three cohorts.
Next figure presents another study and shows HIF1A allele frequency among strength athletes stratified by competitive standard:
This figure shows that allele frequency rises as achievements in power sports increase, supporting the notion that the HIF1A gene variant has a role in promoting strength capabilities.