Genetic Influences on Muscle Oxygen Kinetics & Perforamnce

In discussions about an individual’s oxygen kinetic profiles we’ll often hear talk of different energetic limitations, rates of maximal oxygen extraction, maximal vasodilator capacity of skeletal muscle, and muscle fiber composition. Seldom do discussions of an individual’s genetics come into play. The reasons for this are likely twofold:

  1. Direct-to-consumer genetic testing products are of varying quality, and much of the information gleaned through these services are based on genome wide association studies that have little predictive value for consumers.
  2. The influence of an individual’s genetic makeup on athletic performance is not entirely clear. This is partly due to the fact that a superior genotype does not guarantee a superior phenotype, as discussed in a . This is further skewed by the fact that sports performance is so multifaceted, that the effect or specific genes (or lack thereof) can easily be washed out by other factors that influence performance like environment, hard work, luck, socioeconomic factors, and intelligent training.

However, with the above limitations in mind, there may still be some efficacy in genetic testing for atheltes. Specifically, SNP genotyping which is a measurement of genetic variations in an individual’s single nucleotide polymorphisms (SNPs). SNPs are one of the most common types of genetic variations between individuals of the same species, and the increased interest in SNPs has driven the rapid development of different SNP genotyping methods. One of the first SNPs to gain wide stream attention in the sports performance world were those that code for variations in the angiotensin-converting enzyme, or ACE gene of which there are over 160 known variations. The ACE gene is a central component of the renin-angiotensin system which helps control blood pressure by regulating fluid volume in the body. While this may not seem relevant in the context of sports performance, it has meaningful impacts on . There are three primary ACE genotypes that have the following effects:

  1. DD Genotype — this genotype is associated with high plasma levels of the ACE protein. individuals with this genotype will have a higher capacity to produce angiotensin II, which will cause a premature and excessive increase in blood pressure, resulting in a lower maximal heart rate and a lower VO2max.
  2. DI Genotype — this genotype is associated with intermediate levels of the ACE protein. Compared to the DD genotype, individuals with the DI genotype have an increased maximal heart rate and greater maximum oxygen consumption (VO2max). Additionally, individuals with the I-alleles show enhanced endurance performance compared to individuals to the D-allele.
  3. DII Genotype — this genotype is associated with low levels of the ACE protein. As with the DI genotype, individuals with the DII genotype show enhanced maximum oxygen consumption and endurance performance. Because these individuals have two I-alleles these effects are even more pronounced.

Unsurprisingly, the I-allele (DI and DII genotypes) are found with an increased frequency in elite endurance athletes, whereas the D-allele (DD genotype) is found with increased frequency among elite athletes in speed and power oriented sports. However, we can’t chalk performance up to one SNP alone, and in reality we are likely just scratching the tip of the iceberg as it relates to identifying genetic markers associated with elite performance in different sports disciplines. For example, in more recent years evidence has emerged showing that the ACTN3 gene, which codes for different forms of the alpha-actinin-3 protein, has even greater predictive strength for endurance performance than does the ACE gene. Interestingly there even appears to be phenotypical effects associated with different combinations of ACE and ACTN3 genes. For example, having endurance-associated alleles in both genes seems to favor an individual to endurance performance and having strength-associated alleles in both genes favors one to performing well in strength, speed, and power based sports. In a by Hiroshi Kumagai and colleagues it was even demonstrated that different combinations of ACE and ACTN3 genes have a meaningful impact on muscle fiber composition such that individuals with endurance-associated alleles on both genes have a higher proportion of myosin-heavy chain (MHC) isoforms associated with type I muscle fibers. For those interested in learning more about MHC isoforms and their impact on muscle fiber type I recommend Dr. Andy Galpin’s 2012 paper titled, Human Skeletal Muscle Fiber Type Specific Protein Content.

So, how does this all relate back to an individual’s oxygen kinetic profile?

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Evan Peikon is an integrative physiologists with an interest in enhancing human performance. IG: @Evan_Peikon. Website: