The Best WritersGENETICS OF ATHLETIC PERFORMANCEDr. Katie Dabrowski, PT, DPTSome beginning conceptsDarwin’s theory of natural selection = individuals with traits that are favorable are more likely to survive and reproduce.Those who are “stronger” are better equipped to handle struggles of the worldEach individual has a limited capacity to perform exercise but what determines the limit to that capacity?It is proposed that up to 50% of physical fitness is due to geneticsAthletes may be inherently predisposed to be more fitBut there may be a trade-off genetically skilled athletes in one domain may be lesser-than in another domain (a sprinter with power and strength vs. lacking endurance, for example)What genes are responsible for an athlete dominating in one sport (let’s say a sprint) rather than another (like a marathon)?Components of PerformanceBody morphology: Height and body compositionAerobic endurance: Ability to sustain an aerobic effort over time.Requires the ability of the cardiovascular system to deliver oxygen to working muscles, and the ability of those muscles to utilize that oxygenQuantified via VO2max, but other factors like economy and ventilatory threshold influence performance in addition to VO2maxMuscular strength: Ability of muscle to generate force.Quantified via one rep maxCognitive factorsInjury susceptibilityNutritionTrainabilityPerformance Enhancing Polymorphisms (PEPs)PEPs = Genetic variants that, when inherited, can lead to improved athletic performance200+ PEPs existAngiotensin-Converting EnzymeACE gene contains the first PEP to be identifiedACE catalyzes the conversion of angiotensin I into angiotensin II, which affects vasoconstriction and regulation of salt and water homeostasis via releasing aldosteroneACE is also responsible for regulating inflammatory reactions to lung injury, respiratory drive, erythropoiesis, tissue oxygenation, and regulation of skeletal muscle efficiencyAngiotensin-Converting EnzymeMost common polymorphism associated with ACE is of the I alleleThis polymorphism is associated with improved performance in endurance sports due to higher circulating and tissue ACE activityACE polymorphisms and athletic performance were first studied in Australian National Rowers at the pre-Olympic trials in 1996Researchers found significantly increased frequency of I allele in elite rowers compared to normal controlsAnother study investigated the role of ACE polymorphisms on body composition by training men over a 10-week periodIndividuals with the I genotype had a greater anabolic responseAnd another study found a relationship between the I allele and mountaineering individuals who engage in high altitude mountaineering ascending over 8000 meters without supplemental oxygen show an excess in the ACE I allele frequencyACTN3 R577XThis gene codes for an important protein found exclusively in the fast type II muscle fibers used during explosive activitiesA polymorphism resulting in a premature stop codon (X) rather than (R) at position 577The R allele is advantageous in power events, and the RR genotype is overrepresented in elite power athletes; the X polymorphism is associated with lower sprinting ability and muscle strengthA study of elite European athletes found that power athletes are 50% less likely to have the XX genotypeNRF1NRF1 has a role in mitochondrial biogenesis, oxidative phosphorylation, and increased capacity for energy during exerciseA study of Chinese men found two SNPs (single nucleotide polymorphisms) in noncoding regions of NRF1 that were associated with submaximum aerobic capacity (ventilatory threshold)These men underwent a strenuous endurance program for 18 weeks of running, swimming, and cyclingThose without the two SNPs developed significantly better ventilatory thresholds compared to those with the polymorphismsADRB2A study of elite male endurance athletes reported a significant difference in a SNP in the ADRB2 geneSedentary controls had an excess of the Gly allele compared to these elite athletesGly allele is associated with increased body mass index (BMI)Mitochondrial DNAEndurance athletes tend to have enhanced mitochondrial function:Increased mitochondrial gene expressionIncreased mitochondrial DNAIncreased mitochondrial enzyme activityMitochondrial function is linked to aerobic fitness and insulin sensitivityNitric oxide synthaseAt rest, increased nitric oxide (NO) production and NO synthase (NOS) inhibition can increase and decrease, respectively, blood flow to skeletal muscleNO decreases mitochondrial respirationNOS inhibition blocks glucose transport during exercise; NO has the opposite effectNOS3, a polymorphism, is linked to increased adaptability of the heart during exerciseMyostatinMSTN gene gained interest when a 4-year-old German boy who was homozygous for MTSN mutations and displayed significant muscle hypertrophyHe was shown to have very muscular thighs and upper arms at birthUltrasonography showed that his quadriceps muscle was 7.2 SD above the meanHis mother was a former Olympic sprint swimmer and was heterozygous for the same mutationPPARDPPARD (peroxisome proliferator-activated receptor-delta) gene = determinants of mitochondrial functionPPARD:Regulates the gene expression in lipid and carbohydrate metabolismAffects insulin sensitivity by modifying skeletal muscle glucose uptakePolymorphisms in this gene are associated with predisposition to endurance performanceFrequency of PPARD polymorphism in endurance athletes = significantly higher than controlsPGC-1PGC-1 regulates the expression of genes for oxidative phosphorylation and ATP productionMuscle-specific expression of PGC-1 improves performance during voluntary and forced exercise challengesPGC-1 transgenic mice have enhanced performance during peak VO2 testsHIFsHIFs = hypoxia inducible factors (proteins)Help us to understand the body’s response to hypoxia in tissues during increased oxygen demand (muscles working at high intensities)The genes controlled by HIFs include those that:Stimulate red blood cell production*Encode glycolytic enzymes**These things are critical for achieving high levels of anaerobic performanceRemoving HIF causes an adaptive response in skeletal muscle similar to endurance training aka these muscles are no longer able to be powerful and anaerobic with short bursts, but instead perform best with endurance activitiesInjury RiskResistance to and/or the ability to recover from injury is another integral factor for optimal performanceTwo main areas studied for genetic links to injury:ConcussionTendinopathyConcussionAPOE is the gene most frequently studied with regard to concussion/mild TBIIt has three isoforms (ε2, ε3, and ε4 alleles), and the ε4 allele has a strong association with Alzheimer’s diseaseThis association led to many researchers investigating a possible link between this allele and risk for concussion/outcomes after TBISome studies have found that individuals with the ε4 allele suffer worse outcomes from head injury; boxers with the ε4 allele have higher chronic brain injury scoresTendinopathyTendinopathy = pain and pathology associated with overuse in/around tendonsSeveral genes associated with tendon injuriesCOL1A1COL5A1COL12A1COL14A1TNCMMP3TGFB1GDF-5We’ll highlight some of themCOL1A1Collagen type I alpha 1 geneCollagen type I fibrils are a major constituent of bone matrix, forming strong parallel bundles of fibers in tendons and ligamentsA SNP polymorphism of COL1A1 which results in a T to G substitution is associated with osteoporotic fracture, osteoarthritis, myocardial infarction, lumbar disc disease, and stress urinary incontinenceTT genotype = reduced risk of cruciate ligament ruptures and shoulder dislocation ruptures compared with GG genotypeTNCTenascin C geneAssociation of ABO blood group with Achilles tendon injuryO blood = more susceptible to tendon injuriesTNC gene is closely linked to the ABO gene that determines blood type