The athletic potential is multifactorial; gender, age, specific discipline, weight, body composition, and genetics are strong predictors of performance and endurance. Nonetheless, exercise and continuous training increase reactive oxygen species (ROS) levels, and our body has to recover by activating antioxidant enzymatic complexes. In a molecular contest, performance is supported by a carefully orchestrated cascade reaction starting in the cellular nucleus. Therefore, genetic profiling can fill the knowledge gap to increase an athlete’s performance by determining genetic limitations and advantages. Nutritional support and recovery training is needed to replete these mechanisms to build up stamina and improve the athlete’s performance. 

Recovery encoding genes

 After a training session, antioxidant enzymes like superoxide dismutase (SOD), Catalase (CAT), and Glutathione (GPx) levels become depleted. Furthermore, these enzymes are part of a cascade reaction initiated by nuclear transcription factors. Without this initiating mechanism, the antioxidant enzyme pathway and release would not be possible.

Gene variation for energy and endurance:

• NRF2:  

  NRF2 gene encodes for Nuclear factor erythroid 2-related factor. This transcription factor has a cellular protective effect in response to oxidative stress. Furthermore, Nrf2 improves the energy production rate and respiratory capacity, and the formation of new mitochondria.

Up until 2016, no investigation could show the impact of Nrf2 on muscle endurance and mitochondrial upregulation. However, a study performed on rats was able to convey the molecular mechanism behind it. This study found that the absence of Nrf2 translated into a 40% reduction in state 4 respiration and a 68% increment of ROS in those KO mice. 

Studies report that a G allele in the encoding gene for Nrf2 is associated with elite endurance performance in the sport context. Although the G allele is extremely rare, the literature associated it with an improvement of 50-60% in VO2 max.

• PPARGC1A: 

   This is the gene that encodes for Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). Considered and a coactivator of transcription, PPAR-y participates in multiple mechanisms that involve the skeletal muscle, such as:

1. Mitochondrial biogenesis.
2. Glucose utilization.
3. Fatty acid oxidation.
4. Gluconeogenesis.
5. Insulin signaling.
6. Thermogenesis.

The metabolisms improvement of substrates like glucose and lipids induced by PPARGC1A supports muscle fiber oxidative capacity by increasing mitochondrial number and power. However, this improvement is only possible through the upregulation of respiratory factors Nrf2 and Nrf1. 

Furthermore, the Nrf2 and Nrf1 respiratory factors upregulate the transcription of respiratory genes and increase the expression of the mitochondrial transcription factor A (TFAM). Therefore, there is an apparent pathway reaction among PGC-1α–NRF–TFAM, which results in the regulation of exercise-induced changes in muscle fibers.

 PGC-1α is also a coactivator of different proteins by the myocyte enhancer factor 2 (Mef2). In turn, these proteins are crucial for exercise-induced muscle fiber differentiation.

The GG genotype in the PGC-1α gene has been associated with greater mitochondrial biogenesis, reflecting a more significant muscle power and aerobic capacity. This polymorphism in athletes is strongly related to several cardiorespiratory fitness phenotypes that image more extraordinary endurance performance.

• PPARA: 

  PPARA is the encoding gene of PPAR-a. An increased level of PPAR expression mainly occurs in those tissues that metabolize high amounts of an energetic substrate such as lipids and carbohydrates. Furthermore, these tissues, such as the liver, muscle, brown adipose tissue, heart, and kidneys, play an essential role in endurance performance and function.

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The genetic applications in sports and PPARA have been studied in-depth. Some reports show that a C allele in this encoding gene is associated with strength and muscle contraction power in soccer players. This SNP is common in those athletes with an elite status when compared to the sub-elite group. On the other hand, a G allele had a strong relation with endurance due to the use of fatty acids to produce ATP and greater aerobic capacity.

The strong relation between coactivators and nuclear transcription encoding genes translates to muscle power, energy metabolism, and respiratory endurance in athletes. An athlete can improve performance by detecting limiting gene factors and doing the proper training, nutritional, and lifestyle changes. These specific gene variants relate to how muscle fibers can change with exercise and nutrition. PPAR is retinoid dependent, meaning that Vitamin A plays a critical role in its upregulation.- Ana Paola Rodríguez Arcinega, MS

References:

Crilly, Matthew J et al. “The role of Nrf2 in skeletal muscle contractile and mitochondrial function.” Journal of applied physiology (Bethesda, Md.: 1985) vol. 121,3 (2016): 730-40. doi:10.1152/J Appl Physiol.00042.2016

Yvert, Thomas, et al. “PPARGC1A rs8192678 and NRF1 rs6949152 Polymorphisms Are Associated with Muscle Fiber Composition in Women.” Genes vol. 11,9 1012. 27 Aug. 2020, doi:10.3390/genes11091012

Petr, Miroslav et al. “Association of Elite Sports Status with Gene Variants of Peroxisome Proliferator-Activated Receptors and Their Transcriptional Coactivator.” International journal of molecular sciences vol. 21,1 162. 25 Dec. 2019, doi:10.3390/ijms21010162

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