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The Genetics of Athletic Performance
Ian Craig, BSc MSc CSCS
Daniel Meyersfeld, PhD
Introduction
Every athlete seeks a competitive edge. In sports, it is recognised that good coaching practices are comprised
of a mixture of art and science. Scientifically, training theories include progressive overload, super
compensation and training-recovery ratios: they have been well studied and are clearly understood. Up until
now however, what scientific research within sport has generally lacked, is the individuality required by each
athlete to attain optimal fitness and performance. Within the coaching realm, this individuality is generally
considered within the art of coaching and includes the ability to recognise training practices that may work
well for one athlete, but don't necessarily work well for another.
Science is thankfully now starting to catch up with the individuality needs of training provision; i.e. the art of
training. Since 2003, when the human genome was finally mapped to completion, research within the genetics
of sporting performance has been prolific. It is now thought that a high percentage of the variance in athlete
status is explained by additive genetic factors. For instance, Ahmetov et al (2009) looked at multiple genes and
endurance performance in 1423 Russian athletes, compared to 1132 controls and found that 66% of the elite
endurance athletes were carriers of 8 or more of these endurance-related alleles. This genetic predictability of
sporting prowess is only likely to increase in years to come as more and more genes are studied and
understood.
Genes have now been coded and studied that can tell an athlete or their coach whether they should be
training towards a power or an endurance sport, how quickly they are likely to recover from training sessions,
and their genetic susceptibility for tendon and other soft tissue injuries. It is a contemporary notion that
prescription exercise regimes can potentially be tailored to the genotype of the individual. A Rugby League
team in Manly, Australia have claimed that they gained a competitive advantage over their rivals by using
genetic testing to personalise the design of their players’ training programmes (Dennis 2005). The interest in
genetics within the field of sport and exercise lies with talent spotting and understanding the training potential
of an individual. Although there are ethical considerations around the topic of talent searching, genetic testing
can allow individual athletes, who are dedicated to their sport, to learn more about the training patterns that
will help them progress towards their genetic potential.
Genetic Expression
Athletic success is not just about genetic predisposition. The athletic phenotype is a complex manifestation of
many genetic and environmental exposures. Some genes have a direct effect on physical attributes, whereas
others have an indirect effect via gene-gene or gene-environment interaction. Athletic performance therefore
results from firstly choosing the right sport for your genetic type and secondly, the right training, lifestyle,
nutrition and environmental interactions to optimally express your inherited genes.
Genetic loci have been linked to VO2max, VO2max training response, stroke volume, cardiac output, blood
pressure during exercise, body composition changes with training, plus insulin and glucose responses to
habitual exercise (Brutsaert & Parra 2009). As research unfolds, single genes will still probably only explain a
small part of the variance reported for a particular athletic trait: there are just so many other interacting genes
and environmental exposures at play.
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Trainability of Genes
Exercise training affects the way that our genes are expressed; i.e. switched on and off. For example, acute and
chronic training can influence the body’s insulin resistance, glucose metabolism and use of fats for energy. A
training programme can also attenuate the inflammatory response that occurs after an exercise bout, thereby
improving speed of recovery and also increase an individual’s antioxidant profile and provide more
physiological support to the stresses of training.
Additionally, the fact that exercise training can augment aerobic and anaerobic capacity, muscular strength
and endurance, power, cardiovascular health and numerous other physiological variables (McCardle et al
1991; Powers & Howley 1990) is well accepted. The degree of physiological adaptation that results from
training is now of more interest to us. As will be noted in the following reviews of exercise-oriented genes,
training responses can vary widely based on an individual’s genetic make-up, with athletes who have one
genotype responding more similarly to training compared to those with different genotypes (Bouchard et al
1997). If coaches and athletic practitioners have more understanding of what type of training (plus nutritional
and lifestyle patterns) their athletes are most likely to respond to, it will help them to design an optimal
training programme.
“With population turnover, World and Olympic records should improve even without further enhancement of
environmental factors, as more advantageous polygenic profiles occasionally, though rarely, emerge.”
Williams and Folland (2008)
Sporting performance genes
The DNAlysis DNA Fit profile tests for genes in three categories that relate to sporting performance: 1) Power
and Endurance, 2) Tendon Pathology and 3) Recovery.
1) The Power and Endurance section tests genes that code for physiological factors such as circulation,
blood pressure control, strength, cardio-pulmonary capacity, mitochondrial synthesis, muscle fibre type
specialisation, muscle fibre hypertrophy, cardiac output, muscle metabolism and adaptability to training
regimes.
2) The Tendon Pathology section examines genes that are involved in the structural integrity of soft tissues
in the body. Certain polymorphisms implicate predisposition to tendon injuries (including Achilles
Tendonitis), plus ligament, cartilage and bone pathology.
3) The Recovery genes are the best example within this genetic panel of the need to integrate training and
nutritional advice when supporting an athlete’s health and fitness. The featured genes consider disposition
to inflammation and free radical stress within the body, which may imply the need for more focussed
nutritional support, along with extended recoveries between training repetitions and sessions.
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Genetic Variants Associated with Power and Endurance
It is now more than a decade since the first gene was identified as an indicator of sporting performance
(Montgomery et al 1998). This gene, ACE, has now been extensively studied and been shown to be predictive of
endurance or power-oriented performance.
Numerous other genes have also been studied and according to Ahmetov & Rogozkin (2009), 36 genetic
markers have been associated with endurance and power athlete status. Thirteen such genetic polymorphisms
have been included in the DNA Fit test: they have been identified as those with high scientific credibility and
those which can make a difference to the training and lifestyle intervention of an athlete, based on knowledge
of his/her genes.
Gene Name: Angiotensinogen (AGT)
Polymorphism: Met235Thr
Function: Angiotensinogen is a protein that is produced mainly by the liver. Plasma angiotensinogen levels are increased
by corticosteroids, oestrogen, thyroid hormone, and angiotensin II. It is a precursor of angiotensin, which causes
vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. Like the ACE gene, AGT
plays an important role in the renin-angiotensin system.
Polymorphism: Allele C encodes for a threonine instead of methionine in codon 235 of the gene. This variant is associated
with higher plasma angiotensin levels and ultimately elevated blood pressure, leading to increased risk for
hypertension-associated disorders. The C allele has been associated with elite power sports performance.
Research: When genotyping top athletes, Gomez-Gallego et al (2009a) showed that the CC genotype was significantly
more represented in power athletes (34.9%) than the control group (16%) and top endurance athletes (16%). Like the ACE
DD genotypes however, AGT CC homozygotes should be aware that they are genetically more susceptible to left
ventricular cardiac development with training (Pelliccia & Thompson 2006; Karjalainen et al 1999).
It has been estimated that genetic determinants may explain up to a quarter of the variability in left ventricular
dimensions (Pelliccia & Thompson 2006). When studying the ACE and AGT genes together, it appears that the ACE DD and
AGT CC combination increases left ventricular mass in athletes more than all other genotype combinations (Diet et al
2001): a synergistic effect between the ACE and AGT genes therefore seems to exist.
Rankinen and colleagues (2000) found that when 476 sedentary people were put through 20-weeks of exercise training,
those individuals with the TT genotypes showed an overall decrease in diastolic blood pressure during the training
programme, which greatly exceeded the blood pressure changes in CC genotypes. Additionally, in a longitudinal study of
TT homozygotes, it was demonstrated that regular moderate-intensity exercise attenuates age-related increases in
systolic blood pressure (Rauramaa et al 2002).
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Gene Name: Alpha-actinin 3 (ACTN3)
Polymorphism: 577 R/X
Function: Alpha-actinins are a family of actin-binding proteins that maintain the cytoskeleton. The ACTN3 gene encodes
alpha-actinin 3, which is only present in type II (fast) muscle fibres and also has a low expression in brain tissue.
Alpha-actinins are found at the Z-line of the muscle where they anchor actin filaments and help to maintain the structure
of the sarcomere. Alpha-actinins also interact with a signalling factor that plays a role in the specialisation of muscle fibre
type, diameter and metabolism.
Polymorphism: The ACTN3 gene contains a polymorphism which results in two versions of ACTN3: a functional R allele
and a null X allele. The genotype that is homozygous for the X allele (XX) is completely deficient in alpha-actinin 3. The
percentage of people with two X alleles range from about 1% in African populations to about 18% in Europeans and 25%
in East Asians.
Research: It has been demonstrated that male and female elite Sprint athletes have significantly higher frequencies of the
R alleles than endurance athletes and sedentary controls (Eynon et al 2010a; Yang et al 2003). Additionally, when Roth et
al (2008) studied elite and local black and white bodybuilders, they showed a significantly lower XX frequency in the
bodybuilders compared to controls. None of the black bodybuilders were homozygous for the X allele. In a cycling study,
it was found that subjects who were not ACTN3 deficient had greater peak power outputs and ventilatory thresholds than
cyclists with the XX genotype (Gomez-Gallego et al 2009b).
When studying the ACTN3 gene for endurance performance, mixed results have been found. Shang et al (2010) showed
that the XX genotype was significantly over-represented in the female endurance athletes compared to controls.
However, no relationship between genotype and endurance-status was found in the male athletes. Doring et al (2010)
found that the XX genotype was similar in prevalence between 316 endurance athletes and 304 controls. Additionally,
Saunders et al (2007) found when studying 457 male Ironman triathletes compared with 243 controls, that the XX
polymorphism was not associated with ultra-endurance performance.
These observations have also been replicated in professional cyclists and Olympic endurance runners (Lucia et al 2006).
Collectively these studies suggest that the XX genotype has not yet been shown to be a good marker for endurance
performance.
Gene Name: Bradykinin Receptor B2 (BDRKB2)
Polymorphism: Rpt Seq Exon 1
Function: Bradykinin is an endothelial dependent vasodilator and acts via the Bradykinin B2 receptor. The B2 receptor
forms a complex with angiotensin converting enzyme (ACE) and this is thought to play a role in cross-talk between the
renin-angiotensin and the kinin-kallikrein systems.
Polymorphism: The absence of a 9-base pair (bp) repeat on exon 1 (-9) is associated with increased Bradykinin B2 mRNA
expression, which is thought to increase the efficiency of muscular contraction (i.e. the amount of energy used per unit of
power output). What’s more, the +9 allele was associated with increased thirst and fluid loss, which would make it a
handicap for endurance sports.
Research: When 115 healthy men and women were compared with 81 Olympic track athletes, Delta efficiency of muscular
contraction was significantly associated with the BDKRB2 genotype: the efficiency of individuals homozygous for the -9
alleles was better than the +9-9 genotype, which in turn was better than the +9+9 genotype (Williams et al 2004). There
was also evidence for an interaction with the ACE genotype, with individuals who were ACE II and BDKRB2 -9-9, having the
highest Delta efficiency values.
When Ironman triathletes were studied (Saunders et al 2006a), the BDKRB2 -9-9 genotype occurred at a significantly
higher frequency in the triathlete group compared to controls. The same investigators (Saunders et al 2006b) found that
the BDKRB2 +9+9 genotype was associated with greater fluid weight losses during the Ironman triathlon, which would put
competitors at a disadvantage.
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Gene Name: Beta 2 Adrenergic Receptor (ADRB2)
Polymorphism: Arg16Gly / Gln27Glu
Function: The ADRB2 gene encodes for Beta 2 Adrenergic receptors, which play a part in the regulation of cardiac,
pulmonary, vascular, endocrine functions and the central nervous system. Adrenaline, predominantly via the Beta 2
adrenergic receptors, plays a major role in maintaining blood glucose levels by promoting glycogenolysis during
prolonged exercise.
Polymorphism: Arg16Gly - a polymorphism between arginine and glycine in position 16 of the gene has been associated
with altered vasodilator responses to catecholamines during stress, and so modulates the pressor response (increasing
cardiac output), as driven by the sympathetic nervous system.
Gln27Glu - a polymorphism between glutamine and glutamate at position 27 of the gene has been associated with
endurance performance and also the ability to lose weight as a result of an exercise programme.
Research: Arg16Gly - When researching airway tone, Snyder et al (2006) found that the genotype didn't influence lung
function during exercise, but the Arg16 carriers had a rapid pulmonary recovery to baseline afterwards, whereas the Gly16
homozygotes had persistent bronchodilation during recovery. Tsianos et al (2010) found that ArgArg genotypes had faster
marathon running times compared to Gly carriers and also that the Arg polymorphism was associated with lower blood
pressure at rest, during and after exercise. In line with this observation, it has also been shown that an excess of Gly
carriers have been found in sedentary populations compared with elite endurance athletes (Wolfarth et al 2007). With
regards to ADRB2 gene effect on sympatho-excitation, the heart rate at fatigue after a handgrip exercise was greater for
Gly16 than for Arg16 genotypes (Eisenach et al 2004). The authors suggested that the Gly16 carriers may be better at a
pressor response in the face of increased peripheral vasodilation.
Gln27Glu - Moore et al (2001) showed that the Glu27Glu genotype was almost absent in postmenopausal athletes.
Additionally, weight and BMI tended to be higher in the Glu27Glu women and VO2max was lower than other genotypes.
This research was supported by McCole et al (2004), who found that in 62 postmenopausal women undergoing habitual
physical activity, the highest observed sub-maximal exercise arterio-venous O2 difference (a-vDO2) was observed in
women homozygous for the Gln allele compared to the Glu genotype. This polymorphism has also been linked to fat
deposition in women: 10 obese women with the Gln27Gln genotype were compared to 9 matched women with the
Glu27Glu genotype. Lipolysis and fat oxidation during an exercise test appeared to be blunted in the Glu27Glu group
(Macho-Azcarate et al 2003).
Gene Name: Thyrotropin Releasing Hormone Receptor (TRHR)
Polymorphism: rs16892496 / rs7832552
Function: The TRHR gene encodes the Thyrotropin-releasing hormone (TRH) receptor. TRH is a hormone that stimulates
the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary. TSH in turn stimulates the
release of Thyroxin (T4) and Triiodothyronine (T3) from the thyroid gland. T3 and T4 increase metabolic rate, help
catecholamines to mobilise fuels during exercise and are involved in growth (Powers & Howley 1990).
Polymorphism: The two polymorphisms studied (rs16892496 and rs7832552) are significantly associated with lean body
mass (skeletal muscle mass). The homozygous arrangements of the minor allele (in 7% of the population) on each of the
two polymorphisms (rs16892496 GG and rs7832552 TT) are favourable for increased lean body mass and therefore
strength and power.
Research: In a study of 1000 Caucasians (Liu et al 2009), subjects carrying the major alleles for the two different SNPs
(rs16892496 T and rs7832552 C), had 2.7kg and 2.55kg lower lean body mass respectively. This study was replicated by the
same research team with more than 6000 Caucasian and Chinese subjects and consistent associations of lean body mass
were observed (Liu et al 2009). These findings were supported by Roth (2011), who said that TRHR was associated with
skeletal muscle strength, just like ACE, ACTN3, CNTF and VDR genes and therefore had implications for sarcopenia.
Additionally, Liu and colleagues (2009) explored the interactions between TRHR and certain genes involved in the growth
hormone and insulin-like growth factor pathways: tentative connections were indicated.
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Gene Name: Nuclear Respiratory Factor 2 (NRF-2)
Polymorphism: rs7181866
Function: The NRF-2 gene codes for the NRF-2 protein that improves respiratory capacity and increases the rate of ATP
production during exercise. It is important in the induction of mitochondrial biogenesis and also regulates several genes
that encode mitochondrial proteins: these include cytochrome C and TFAM. NRF-2 also regulates heme biosynthesis.
Polymorphism: The very rare G allele of the NRF-2 gene is associated with greater improvements in VO2max with an
endurance training programme: around 50 to 60% better results. However, the AA genotype makes up approximately 98%
of the population.
Research: Eynon et al (2009a) found a significantly higher proportion of the AG genotype (than the AA) in endurance
athletes (12%) compared to sprinters (2%) and control subjects (2%): This association was even more pronounced when
looking at elite International athletes. In an investigation by He et al (2007), the effects of training on running economy
were studied with respect to the NRF-2 gene. When three SNPs on the NRF-2 gene (rs7181866, rs12594956, rs8031031)
were considered, a particular genetic combination was shown to have a 57% higher training response in running economy
than non-carriers of the particular alleles. Researchers concluded that polymorphisms on the NRF-2 gene may explain
some of the between-person variance in endurance capacity.
Gene Name: Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1 (PPARGC1A)
Polymorphism: Gly482Ser
Function: PPARGC1A (otherwise known as PGC-1alpha) is a co-activator of PPAR-gamma and other nuclear hormone
receptors and plays an essential role in energy homoeostasis. It is involved in mitochondrial biogenesis, fatty acid
oxidation, adipocyte differentiation, glucose utilisation, thermogenesis, angiogenesis and muscle fibre type conversion
towards type I fibres. It is expressed in tissues with high energy demands and is therefore abundant in mitochondria and is
consequently associated with endurance performance.
Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. It appears that the activation of
PPARGC1A may mediate the initial phase of the exercise-induced adaptive increase in muscle mitochondria. Additionally,
the subsequent increase in PPARGC1A protein sustains and enhances the increase in mitochondrial biogenesis that is
associated with exercise training.
Polymorphism: The serine allele (SerSer or GlySer genotype) is associated with lower levels of PPARGC1A and
consequently reduced aerobic improvements with exercise training when compared to the glycine (Gly) allele. The serine
allele may also increase the possibility of raised blood pressure.
Research: Eynon et al found that PPARGC1A GlyGly genotypes were more frequently found in elite endurance athletes
compared to sprinters and control subjects (2009b, 2010b). Additionally, Lucia et al (2005) demonstrated that the
frequency of the serine allele was significantly lower in world class Spanish endurance athletes than in controls.
In 2007, Stefan et al looked at the relationship between the PPARGC1A gene and insulin sensitivity with exercise training:
after nine months of training, individuals with the serine-encoding allele in their PPARGC1A gene experienced lower
increases in anaerobic threshold compared to individuals who were homozygous for the glycine alleles.
Additionally, those serine-carrying individuals who also carried the minor G allele of the related PPARD gene had less
increases in insulin sensitivity after the training programme. In relation to gene expression, the PPARGC1A gene has also
been shown to be stimulated by insulin and decreased by ageing (Ling et al 2004). Presence of the serine allele has also
been associated with increased blood pressure, but this has only been noted in younger adults (Vimaleswara et al 08).
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Gene Name: Peroxisome Proliferator-Activated Receptor-Alpha (PPARA)
Polymorphism: Intron 7 G/C
Function: PPAR-alpha is a transcription factor and a major regulator of lipid and glucose metabolism in the liver, skeletal
muscle and heart. It is also involved in energy homeostasis. PPAR-alpha is activated under nutrient-deficient conditions
and is necessary for the process of ketogenesis, a key adaptive response to conditions of low carbohydrate availability.
Activation of PPAR-alpha promotes uptake, utilisation, and catabolism of fatty acids by up regulation of genes involved in
fatty acid transport and peroxisomal and mitochondrial fatty acid metabolism. Endurance training increases the use of
non-plasma fatty acids and may enhance skeletal muscle oxidative capacity by influencing PPARA gene expression.
Polymorphism: the PPARA G allele is associated with endurance performance and type I muscle fibre specialisation: for
example G allele frequencies have been shown to be higher in endurance-orientated compared to power-orientated
athletes and GG homozygotes are thought to have significantly higher percentages of slow twitch fibres compared to CC
homozygotes. Like the D allele for ACE, the PPARA C allele has been associated with higher left ventricular growth after
training and there are is also an association of the CC genotype with power in sports.
Research: It was shown that the frequency of the G allele was significantly higher in Russian endurance-orientated
athletes (80.3%) compared to power-oriented athletes (50.6%) [Ahmetov et al 2006]. It was also noted that the mean
percentage of type I muscle fibres was higher in GG homozygotes than CC genotypes (55.5 vs. 38.5%). The same authors
(Ahmetov et al 2007) also found that the frequencies of the PPARA G alleles in 205 elite rowers were significantly greater
than in control subjects (90.1 versus 83.6%), plus the G alleles were associated with higher values of aerobic performance.
In a study of 193 Lithuanian elite athletes, Gineviciene and colleagues (2010) found that the PPARA C allele was more
common in the mixed athlete group (endurance, mixed sports, speed/power and team sports) than in the general
population plus the PPARA CC genotype was associated with muscle mass and single muscular contraction power,
whereas the GG genotype was more related to endurance sports.
Exercise-induced left ventricular growth has been associated with the PPARA C allele (Jamshidi et al 2002): individuals
homozygous for the C allele had a 3-fold greater and heterozygotes had a 2-fold greater increase in left ventricular mass
than G allele homozygotes. The investigators suggested that the hypertrophic effect of the rare C allele is due to
influences on cardiac substrate utilisation.
Gene Name: Vascular Endothelial Growth Factor (VEGF))
Polymorphism: -634CG
Function: VEGF is an endothelial cell proliferator involved in angiogenesis (blood vessel growth) to match the needs of the
active tissue. VEGF levels therefore affect peripheral circulation and capillary blood flow, increasing oxygenation and
impacting on VO2max. Muscle VEGF levels can increase up to 4-fold in response to training.
Polymorphism: The CC genotype of the VEGF gene is associated with higher VEGF levels and increased VO2max levels at
baseline plus a better VO2max response to training. No differences have been reported in strength gain between
genotypes, which suggests that the higher VEGF producers (CC genotype) experience an increase in muscle efficiency with
no change in muscular strength or power.
Research: The frequency of the VEGF C allele was found to be significantly higher in endurance athletes compared to a
control group and this relationship was even more pronounced with increasing sports standard (Ahmetov et al 2008).
These researchers found a correlation between the C allele and maximum power, VO2max and maximum lactate levels in
athletes. This observation was supported by Prior et al (2006), who agreed that the C allele was associated with endurance
performance and VO2max. In terms of the VEGF response to exercise, Coffey et al (2006) noted a 4-fold increase in VEGF in
athletes during a 1-hour cycle bout at 70% peakO2. In a study of ischaemia, Gustafsson et al (2005) guided 9 subjects
through 45 min of single-leg knee extensions: once normally and once with blood flow restriction to induce ischaemia.
VEGF increased significantly after exercise with the reduced blood flow.
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Gene Name: Vitamin D Receptor (VDR)
Polymorphism: Taq1 / Fok1
Function: The VDR gene encodes the nuclear hormone receptor for vitamin D3 and is expressed by cells in most organs.
VDR activation in the intestines, bones, kidneys and parathyroid glands leads to the maintenance of calcium and
phosphorus levels in the blood and bone homeostasis. VDR is also involved in cell proliferation and affects the immune
system, organ maintenance and even lipolysis and insulin secretion. Stress hormones such as cortisol are known to
decrease the expression of VDR.
Polymorphism: Taq1 - The nomenclature of the VDR Taq1 gene is TT/Tt/tt (or TT/TC/CC in some papers), where t (C) is the
minor allele. The ‘T’ is named after the Taq1 enzyme. The Taq1 is more-or-less 100% linked with the VDR Bsm1 SNP, so
often information from the literature for one will infer information for the other – the ‘T’ allele on Taq1 is equivalent to
the ‘b’ allele on Bsm1 and vice versa. Only Taq1 is tested by the DNA Fit analysis, but Bsm1 is commonly referred to in the
literature. The Taq1 tt homozygotes have shown better baseline strength and muscle torque in various muscles tested.
The tt genotypes have also have been shown to have higher fasting glucose and insulin levels when physical activity was
low, but this was responsive to training adaptations.
Fok1 - The nomenclature of the VDR Fok1 gene is FF/Ff/ff (or CC/CT/TT), where f (T) is the minor allele. The ‘F’ is named
after the Fok1 enzyme. The FF genotype has been associated with greater strength and gains in bone mineral density with
exercise, but the literature can be quite confusing in this regard.
Research: Taq1 - Roth (2011) noted that vitamin D deficiency has been consistently associated with lower muscle strength.
One study of 501 elderly women (Geusens et al 1997) found that the bb (TT in Taq1) genotypes had a 23% higher
quadriceps strength and 7% higher grip strength than the BB genotypes. In contrast, another study looking at 175 young
women (Grundberg et al 2005) found greater hamstring isokinetic strength in the BB (tt in Taq1) genotype group.
Additionally, in 109 young Chinese women (Wang et al 2006), the bb carriers demonstrated lower knee flexion concentric
torque than the B allele carriers. In 253 men and 240 women (Windelinckx et al 2007), the BB homozygotes had higher
isometric and concentric quadriceps strength than the b allele carriers.
Fok1 - In a study of 206 healthy men and women (Rabon-Smith et al 2005) who undertook 5-6 months of either aerobic or
strength training, it was found that the Ff heterozygotes from the strength training group obtained a significantly greater
increase in femoral neck bone mineral density compared to f homozygotes. The evident importance of the F allele in
adaptation to strength training was supported by a Japanese study (Nakamura et al 2002), within which athletes with the
FF genotype, but not those with the Ff genotype, had increased spinal volume, lumbar spine and femoral neck bone
mineral density when compared to controls. The authors suggested that individuals with the FF genotype adapt to impact
loading by producing stronger bone structure than those with the Ff genotype.
In terms of muscle strength, in contrast to the bone density results, the ff genotype appears to be more favourable.
Hopkinson et al (2008) showed that chronic obstructive pulmonary disease patients who were FF homozygotes had less
quadriceps strength than subjects with one or more f allele. Additionally, Windelinckx et al (2007) showed that quadriceps
isometric and concentric strength were higher in females who were ff homozygous, compared to F allele carriers.
Gene Name: Angiotensin I-Converting Enzyme (ACE)
Polymorphism: Ins(I) / Del(D)
Function: ACE is the most studied of all the genes involved in sporting performance. As shown in the diagram below, it is
an enzyme that hydrolyses angiotensin I into angiotensin II, an important vasoconstrictor of the renin-angiotensin system
and an aldosterone-stimulating peptide. Through its vasoconstricting role, along with the fact that it can deactivate
bradykinin (a potent vasodilator) ACE plays an important role in blood pressure regulation. In normal individuals, plasma
ACE levels can have as much as a 5-fold inter-individual variation and approximately half of this variation is thought to be
due to a polymorphism on the ACE gene.
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Jones et al (2002)
Angiotensinogen
Renin
Angiotensinogen I
ACE
Inactive Fragments
Bradykinin
Vasodilatation:
Increased muscle glucose uptake. Increased
myocardial glycogen and energy rich
phoshate stores.
Angiotensinogen II
Vasoconstriction:
Salt and water homeostasis via Aldosterone
Induction of endogenous growth factors with
increased endothelial, cardiac and VSMC growth
Polymorphism: There exists an insertion/deletion (I/D) polymorphism on Intron 16 of the ACE gene: the I allele is
associated with lower ACE activity. The frequency of the ACE alleles in a UK study was shown to be II (24%), ID (50%) and
DD (26%), although the D allele is higher in Nigerian and Afro-Caribbean populations, whereas the I allele is more
common in Pima Indians and South Asians. The II genotype is an endurance profile, associated with increased muscle
Delta Efficiency with aerobic type exercise or higher repetition weight training and there is less expectancy for muscle
growth. When the ACE I allele and BDRKB2 -9 allele are both present, there seems to be an additive effect on endurance
capacity. The ACE I genotype has been associated with an increased percentage of slow twitch type I fibres, higher
VO2max, greater aerobic work efficiency, improved fatigue resistance, higher peripheral tissue oxygenation during
exercise, greater aerobic power response to training, greater cardiac output and maximal power output in athletes
(Ahmetov & Rogozkin 2009). The DD genotype is a power profile, associated with greater muscle growth with weight
training and being better at strength sports. Higher circulating ACE levels have been significantly correlated with
isometric and kinetic quadriceps muscle strength. Individuals with this genotype should be aware of left ventricular
hypertrophy as a result of exercise training and would be advised to monitor exercise intensity. Their diet should also be
adjusted for their predisposition to hypertension and glucose dysregulation because they are more prone to fat deposition
in the absence of exercise.
Research: I Allele – Cieszczyk et al (2009) found in 55 male Polish rowers, including Olympic and World champions, that
there was a significantly higher frequency of the I allele compared to control subjects (56 versus 44%). This was supported
by Shenoy et al (2010), who demonstrated a greater frequency of I alleles in Indian triathletes compared to controls. In a
study of football players (Jaffer et al 2009), due the different sporting demands, the ID genotype was more common and
frequency of the II genotype decreased, when compared to endurance runners. Williams et al (2004) found that individuals
who were ACE II and BDRKB2 -9-9, had the highest muscle Delta Efficiency at baseline and these genotypes were
associated with endurance performance in elite athletes. The investigators suggested that at least part of the association
between ACE and fitness phenotypes was through the elevation of kinin activity. In contrast, and as a reminder that
strength and power is important in endurance sport, Gomez et al (2009b) found that world class road cyclists who had the
ACE DD combined with ACTN3 RR or RX genotype, had a higher respiratory compensation ratio compared to other
genotype combinations.
In terms of negative aspects of the I allele, Pescatello et al (2007) found that subjects with low calcium intakes and an ACE
II or ID genotype, experienced post-exercise hypertension after exercise at 60% VO2max. Additionally, it has been shown
that individuals with the I allele had a greater increase in post-exercise creatine kinase than the DD genotypes (Yamin et
al 2007). The authors suggested that the II genotype increases risk for muscle damage, whereas the DD genotype may
have protective effects, which may lie in the role of the renin-angiotensin system in the regulation of exertional muscle
injury.
D allele – Costa et al (2009) have demonstrated an association between the ACE D allele and elite short distance
swimming performance. Additionally, the ACE genotype has been associated with higher levels of lean body mass and
bodyweight in DD genotypes, plus the DD’s had significantly greater quadriceps muscle volume than the II genotypes. In
terms of training, Giaccaglia et al (2008) found that in an 18-month exercise programme with elderly and obese
individuals who completed walking and light weight training, those with the DD genotype had greater gains in knee
extensor strength than subjects with the II genotypes.
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Genetic Variants Associated with Tendon Pathology
Acute and overuse musculoskeletal injuries are often the reason for the limited development or early demise
of many athletic careers. It has been clearly shown, primarily by the work of the Collins group in Cape Town
that our genes interact with susceptibility to injury, particularly of collagenous structures within our connective
network of tissues.
By understanding what structural units are most at risk of injury and how to nourish them through appropriate
training and nutrition, practitioners can make a meaningful difference to an athlete’s training and competitive
experience. Three genetic polymorphisms for tendon pathology are included in the DNA Fit test: they have
been identified as those with strong scientific credibility and those which could make a difference to the
training and nutrition intervention of an athlete, based on knowledge of the genes.
Gene Name: Growth Differentiation Factor 5 (GDF5)
Function: The GDF5 gene encodes for Growth Differentiation Factor 5, a protein that is closely related to the bone
morphogenetic protein (BMP) family and is a member of the transforming growth factor beta (TGF-beta) superfamily.
GDF5 is expressed in the developing central nervous system and has a role to play in the development and healing of
skeletal, joint and soft tissues. GDF5 has therefore been shown to influence the susceptibility to injuries and the ability to
recover from them.
Polymorphism: The TT genotype of GDF5 has been shown to correlate with reduced expression of the GDF5 protein in
human soft tissue. In line with this observation, the major T allele is thought to raise the risk of sports and training injuries,
specifically Achilles tendon pathology by up to 2-fold. In a more medical setting, this T allele has also been linked to
osteoarthritis (critically of the knee) and to an increased risk of congenital dislocation of the hip.
Research: The GDF5 gene has not been studied much in relation to sporting musculoskeletal injuries, but the research that
has been done is quite conclusive and by testing this gene, it is thought to be very unlikely to reveal a false positive result.
In the one study that has related GDF5 to sporting injuries, Posthumus et al (2010) studied 171 subjects from Australia and
South Africa, who had Achilles tendon pathology, compared to 235 asymptomatic controls. They found that the TT
genotype was significantly over-represented in the Achilles tendinitis group, so much so, that individuals with the TT
genotype may have twice the risk of this particular injury.
In a very complementary comment on the Posthumus study in the Rheumatology journal (Scott & Khan 2010), the author
pointed to prior research done on twins that revealed a heritability of 40% for tendinopathy at the lateral epicondyle.
They went on to comment that the tendons from GDF5 knock-out mice contain approximately 40% less collagen than the
wild-type mice and demonstrate significantly impaired healing of tendons, whereas rats that have received a GDF5
transfection, have displayed improved tendon healing.
In the medical realm, a strong association has been found between the GDF5 TT genotype and knee osteoarthritis, an
observation that has been consistent across studies (Vaes et al 2009; Valdes et al 2011). The T allele has also been shown
to be over-represented in cases of congenital dislocation of the hip (Rouault et al 2010).
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Gene Name: Collagen 5 Alpha-1 (COL5A1))
Polymorphism: BstUI RFLP
Function: The COL5A1 gene encodes for the alpha-1 chain of type V collagen, one of the low abundance (minor) fibrillar
collagens. Type V collagen molecules intercalate into the tendon and ligament fibrils where, along with other proteins,
they are thought to play an important role in regulating fibrillogenesis and modulating fibril growth (including fibre
diameter) within tendons and other connective tissue. Type V collagen appears to regulate the assembly of heterotypic
fibers, which are composed of both type I and type V collagen.
Polymorphism: The CC genotype, that represents 11% of the general population, has been found to be less frequent in
individuals with tendinopathies. CC also appears to be associated with a better range of motion, which can potentially
contribute to injury risk. Interestingly, TT genotypes tended to be faster in the running section of a triathlon competition.
Research: Collins and colleagues have noted that variants within the COL5A1 gene (plus TNC and MMP3 genes)
co-segregate with chronic Achilles tendinopathies (Collins & Raleigh 2009). In line with these comments, September et al
(2009) studied 85 Australian and 93 South African patients with tendinopathies and compared them to control subjects.
They found that the CC genotype had significantly less risk of developing Achilles tendinitis compared to other genotypes.
Also, Raleigh et al (2009) have shown that the T allele of COL5A1 significantly interacted with the matrix
metalloproteinase 3 (MMP3) gene to raise the risk of Achilles tendinitis.
In terms of other injuries, Posthumus et al (2009a) found that the CC genotype of the COL5A1 gene was under-represented
in female athletes for anterior cruciate ligament injuries, but not for men. The COL5A1 gene has also been associated with
flexibility: Collins et al (2009) found that the CC genotype was linked to a better range of motion in 119 subjects and that
the genotypic effect became more significant with age. Interestingly, Posthumus et al (2011) noted that running economy
has been shown to improve with increased stiffness (reduced flexibility): in line with this observation, Ironman competitors
were genotyped for the COL5A1 BstU1 polymorphism and it was found that TT genotypes completed the run component
significantly faster than CC homozygotes.
Gene Name: Collagen 1 Alpha-1 (COL1A1)
Polymorphism: Sp1 GT
Function: The COL1A1 gene encodes the major protein component of type I collagen, the main fibrillar collagen found in
most connective tissues, including tendons, ligaments and cartilage. This gene produces a component of type I collagen
chain, which combines with another chain produced by the COL1A2 gene, to make a molecule of type I pro-collagen.
These triple-stranded, rope-like pro-collagen molecules arrange themselves into long, thin fibrils that cross-link to one
another, forming very strong mature type I collagen fibers.
Polymorphism: The C to T substitution on the Sp1 site of the gene has been associated with increased gene expression and
more collagen, which has been speculated to increase the tensile strength of tendons and ligaments. The T allele appears
to be protective for ligament injuries in sport, even though it is a risk factor for osteoporosis.
Research: Collins and colleagues, responsible for much of the research done on the genetics of collagen, have noted that
variants within the COL1A1 gene (plus COL5A1 gene) have been shown to be associated with cruciate ligament ruptures
and shoulder dislocations (Collins & Raleigh 2009).
The same laboratory (Collins et al 2010) showed that the COL1A1 TT genotype was significantly under-represented in
patients with cruciate ligament ruptures, shoulder dislocations and Achilles tendon ruptures. This work was supported by
Posthumus et al (2009b), who demonstrated that the TT genotype was significantly under-represented in the anterior
cruciate ligament group compared with the controls.
The Collins scientists have suggested that the TT genotype appears to be protective against acute soft tissue injuries. A
group in Sweden has also supported this work (Khoschnau et al 2008): in a study of 233 cruciate ligament rupture patients,
126 shoulder dislocation patients and 325 control subjects, the TT genotype was under-represented in injured patients
compared to the controls. Subjects who were homozygous for the C allele (CC) and heterozygous subjects (CT) displayed a
similar injury risk. The results of this study did not appear to be modified by general joint laxity.
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Genetic Variants Associated with Recovery
Although not generally considered within sports science or sports nutrition, systemic inflammation and
oxidative stress that results from heavy training and other lifestyle stresses, can greatly affect an athlete’s
health and rate of recovery between training bouts and sessions. Knowledge of the genes that code for these
two variables can provide athletes with an enormous opportunity to improve their specific health and training
responses via nutrition, stress management and nutraceuticals.
Five genetic polymorphisms for recovery are included in the DNA Fit test: they have been identified as those
with strong scientific credibility and those which could make a difference to the training, nutrition and lifestyle
interventions of an athlete, based on knowledge of their genes.
Gene Name: Interleukin 6 Receptor (IL-6R)
Polymorphism: Asp358Ala
Function: Interleukin 6 receptor (IL-6R) is a type I cytokine receptor, made up of a protein complex consisting of a IL-6
receptor subunit (IL-6R) and a signal transducer (gp130). The IL6R gene specifically encodes this IL6R subunit, which
in-turn influences IL6 cytokine action. Proteolytic cleavage of the membrane-bound IL-6R protein leads to the generation
of a soluble form of the IL-6R (sIL-6R), which is able to bind to IL-6.
The resulting IL-6/sIL-6R complex is also capable of binding to gp130 and inducing intracellular signalling (Rose-John et al
2007), increasing the biological activity and half-life of IL-6 (Gray 2009). The resulting IL-6-induced inflammatory response
has been linked to fatigue during exercise, the ability to recover from training sessions and potentially the risk of
overtraining. Regular exercise reduces baseline long-term inflammatory biomarkers, but single high-intensity exercise
sessions will acutely increase local inflammation.
Polymorphism: An A to C SNP on the IL-6R gene has been shown to have an effect on sIL-6R and consequently IL-6 levels.
Subjects with the CC or AC genotypes may have higher levels of sIL-6R and IL-6, thereby increasing the acute inflammatory
effects of exercise. These genotypes are generally advised to increase their recovery time between training bouts and
training sessions, regularly check their inflammatory biomarkers and increase anti-inflammatory nutrition support.
Research: It has been demonstrated in 70 subjects that C allele carriers for the IL-6R gene have significantly higher
baseline sIL-6R levels (Galicia et al 2004). In African- and European-American subjects, one copy of the C allele has been
shown to cause a 1.06 to 1.15-fold increase and two copies of the C allele caused a 1.2 to 1.43-fold increase in IL-6 levels
(Reid et al 2007). It has been clearly shown that IL-6 levels are increased during acute exercise bouts: during one hour of
cycling at 90% of lactate threshold, Gray et al (2008, 2009) found a 5-fold increase in IL-6 and 1 .2-fold increase in sIL-6R
immediately afterwards.
These levels returned to baseline 1.5 hours after exercise. Robson-Ansley et al (2011) also showed that the plasma
concentrations of IL-6 increased post-exercise when athletes ran at 60% of their vVO2max for 2 hours, followed by a 5km
time trial. In this study, when a carbohydrate drink was ingested during the exercise, post-exercise IL-6 levels were
significantly reduced. The same investigators (Robson-Ansley et al 2009) tracked 13 cyclists who rode 468 km over a
six-day period: IL-6 levels were increased post-exercise on day 1, but remained unchanged at rest for the other five days.
sIL-6R, CRP (C-reactive protein) and creatine kinase where unchanged post-exercise on day 1, but were elevated at
baseline for the rest of the trial. It was demonstrated that sIL6R was significantly correlated with CRP and that these
inflammatory markers may affect subjective sensations of post-exercise fatigue. The investigators concluded that
strenuous, prolonged exercise stimulated an acute-phase inflammatory response, which was maintained throughout the
6-day event.
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Gene Name: C-Reactive Protein (CRP)
Polymorphism: 219 G>A
Function: C-reactive protein (CRP) is an acute-phase protein, which rises in response to inflammation in the body:
interleukin-6 (IL-6) and other inflammatory cytokines trigger the synthesis of CRP and fibrinogen by the liver. Its
physiological role is to bind to phosphocholine, which is expressed on the surface of dead or dying cells in order to
activate the complement system, which is part of the innate immune system. CRP is used as a biomarker for acute or
chronic inflammation. Regular exercise and favourable dietary habits can reduce baseline long-term inflammatory
biomarkers (such as CRP), whereas single high-intensity exercise sessions will acutely increase local inflammation
Polymorphism: The CRP AA genotype, which is only found in 12% of the population, has been associated with lower levels
of CRP compared to carriers of the G allele, who make up the majority of the population (88%).
Research: Obisesan et al (2004) have shown that AA homozygotes have significantly lower CRP levels (40%) than G allele
carriers and that CRP levels decrease significantly with 24 weeks of exercise training and a low-fat diet (although GG
genotypes still had the highest CRP levels). This has been confirmed by Eiriksdottir et al (2009), who found that carriers of
the G allele had significantly higher CRP levels than non-carriers. Kullo et al (2007) have shown that higher circulating
levels of IL-6, CRP and fibronectin are associated with lower VO2max levels after controlling for other variables.
This observation was confirmed by Kuo et al (2007) in a huge study of 1438 healthy adults. When monitoring the recovery
from an Ironman triathlon event, Neubauer et al (2008) found that CRP levels were raised post-exercise, along with
several other immune and inflammatory markers. By 19 days post-event, most markers were back to normal except for
CRP and myoglobin, which were still slightly raised, indicating low-grade inflammation for several days after such a large
exercise bout.
It has been shown by a number of studies (Depner et al 2010; Ross et al 2010) that the inflammation induced by eccentric
exercise is greater during recovery when subjects eat a high-carbohydrate compared to a low-carbohydrate diet. For
example, Depner et al (2010) took 12 subjects through 6 sets of 10 high-intensity eccentric contractions and found that
post-exercise inflammation was reduced on a low-carbohydrate diet, although it is important to remember that a
carbohydrate drink during exhaustive exercise has been linked with a decrease in IL-6 levels (Robson-Ansley 2011).
There has been much research examining the use of antioxidants to decrease inflammation.
For example, Phillips et al (2003) found that after eccentric exercise, subjects consuming antioxidant and fatty acid
supplements had significantly lower levels of IL-6 and CRP. However, Gross et al (2011) has noted that free radicals are
involved in signalling roles during training adaptations and so antioxidant supplements may weaken these signals. There
is currently much controversy in the antioxidant literature, so caution is generally recommended around hi-dose
supplementation long-term (McGinley et al 2009).
Gene Name: Interleukin-6 (IL-6)
Polymorphism: -174 G>C
Function: IL-6 is a cytokine secreted by T cells and macrophages, which stimulates an immune response to trauma such as
strenuous exercise, leading to inflammation in the muscle and fatty tissue. IL-6 stimulates energy mobilisation, causing an
increase in body temperature. IL-6 is also a myokine (muscle cytokine) and regulates the gene for CRP. The immune
system of athletes is affected by the intensity and duration of exercise training - the inevitable muscle damage results in
an inflammatory repair process, which is mediated by inflammatory cytokines such as IL-6. Overtraining syndrome (OTS)
has been hypothesised to be caused by excess cytokine release during exercise, resulting in a chronic inflammatory state.
Polymorphism: The C allele has been linked to an increased IL-6 and CRP response to exercise, which may induce more
pronounced fatigue and prolong recovery times. Perhaps because IL-6 levels are hard to measure in the plasma, there is
some discrepancy in the literature about whether the C or G allele is associated with higher IL-6 levels, although the best
evidence appears to be for the C allele.
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Research: In a study of 54 military recruits during their 8-week basic training, it was noted that acute exercise increased
plasma IL-6 levels more in subjects with the CG genotype compared to GG homozygotes (Huuskonen et al 2009).
Interestingly, subjects with the CG genotype also made the greatest gains in VO2max. In support of this, Yamin et al (2008)
found that subjects with the C allele experienced greater creatine kinase (CK) levels than GG homozygotes (3-times the
risk of a massive CK response) after eccentric training, showing that the C allele may be a risk factor for exercise-induced
muscle injury. The IL-6 gene has been shown to be amongst a number of genes that were predictive of sports performance
(Buxens et al 2011) plus the G allele seems to be most common in power athletes compared to control and endurance
athletes (Ruiz et al 2010), which may be due to improved muscle repair after eccentric exercise (Yamin et al 2008).
Under-performance syndrome (UPS), another name for overtraining syndrome, is thought to be influenced by cytokine
sickness, an over-production and/or an intolerance to IL-6 and other cytokines (Robson et al 2003). This suggestion was
supported by Robson-Ansley et al (2007), who noted that an acute period of intensified training can suppress the innate
immune system and chronically increase IL-6 levels. These elevated cytokines can in-turn increase fatigue and malaise,
which are related to the cytokine theories of UPS. The IL-6 genotype can also influence glucose levels: McKenzie et al
(2004) found that baseline fasting glucose levels were higher in the CC genotype compared to carriers of the G allele: 6
months of aerobic training successfully decreased the glucose area under the curve during an oral glucose tolerance test,
but a significant decrease only occurred in the GG genotype.
Gene Name: Superoxide Dismutase 2 (SOD2)
Polymorphism: C-28T – Val(-9)Ala
Function: The SOD2 gene codes for manganese superoxide dismutase (SOD2), which is a potent free radical scavenger
within the cell, especially the mitochondria. The SOD2 enzyme converts superoxide free radicals to hydrogen peroxide.
The mitochondria is commonly referred to as the workhorse of the cell and is therefore the site of many oxidative
reactions during energy production, so free radicals are generated here. There is evidence that oxidation within the cell
contributes to muscular fatigue and extreme exercise can cause increased lipid peroxidation and depleted levels of
vitamin E. Long-term training can increase base levels of SOD2, whereas short-term bursts of intense activity will increase
oxidative stress.
Polymorphism: The SOD2 C allele has been associated with high oxidative stress biomarkers and people with this
genotype who consume low levels of fruit and vegetables are at increased risk of developing long-term disease. These
levels of oxidative stress can be reduced by a diet that contains antioxidants from fruit and vegetables and ideally also
supplements.
Research: In a study of 231 healthy students (Bastaki et al 2006), it was found that SOD2 enzyme activity was 33% higher in
CT or TT individuals compared to CC individuals and on average, SOD2 activity was 15% higher in females than males. It
has been shown that exercise training favourably increases baseline levels of antioxidant enzymes. Garcia-Lopez (2007)
demonstrated that mRNA levels of catalase, glutathione peroxidise (GP), MnSOD (mitochondrial) and CuZnSOD2
(cytosolic) were increased after 21 weeks of strength training, while endurance training only increased SOD2 and GP
mRNA levels. Mastaloudis et al (2004a) studied 22 runners during a 50 km ultramarathon. There were two groups: placebo
or antioxidant (1g Vit C, 300mg Vit E). F2-isoprostanes, a measure of lipid peroxidation, which were at similar levels
between groups at baseline, increased during the run only in the placebo group. In the same study (Mastaloudis et al
2004b), DNA damage increased mid-race, but returned to baseline 2-hours post-race.
Gene Name: Tumour Necrosis Factor Alpha (TNF)
Polymorphism: G-308A
Function: TNF codes for the pro-inflammatory cytokine, tumor necrosis factor (TNF). It is produced chiefly by activated
macrophages and is a member of a group of cytokines that stimulate the acute phase reaction. The primary role of TNF is
in the regulation of immune cells: it is able to induce fever, apoptotic cell death, sepsis (through IL-1 & IL-6 production),
inflammation and to inhibit tumour growth and viral replication. Like other inflammatory cytokines, TNF levels increase
during and after intensive exercise.
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Polymorphism: A, the minor allele on the TNF gene, has been shown to cause 2-fold greater levels of transcription
compared to the G form. The A allele is therefore associated with increased circulating TNF levels. The AA genotype,
although very rare (2%), has been associated with increases in CRP levels during a 20-week exercise programme: CRP
levels are generally expected to fall with regular exercise training. So an A allele carrier, with greater TNF levels, may
experience increased levels of fatigue and poorer recovery times.
Research: Like other inflammatory cytokines, TNF has been shown to be increased during and after highly-intensity
exercise. During 3 hours of cycling or inclined walking (Moldovea et al 2000), plasma concentrations of IL-1β, IL-6 and TNF
peaked at the end of exercise. IL-1β and TNF were shown to be still elevated 24 hours later. Lakka et al (2006) noted that
prior to a 20-week exercise programme, the AA genotype had greater baseline CRP levels. What's more, the exercise
programme decreased CRP levels less in the AA individuals than other genotypes. Nicklas et al (2005) took 213 older or
overweight individuals with knee osteoarthritis through an 18 month walking and weight training exercise trial. It was
found that walking distance and stair-climb time were better for individuals homozygous for the G allele. Exercise
immunologist, David Nieman and colleagues (2005) demonstrated that carbohydrate intake during 2.5 hours of cycling at
60% maxPower decreased plasma cortisol, adrenaline, IL-6 and IL-10 responses, but did not affect TNF alpha levels.
Summary of Genes and Associations
Gene
Implication
Training & Nutrition Action
Genetic Variants Associated with Power and Endurance
AGT
AGT is a precursor of angiotensin, which causes
vasoconstriction and increased blood pressure.
The C allele has been associated with power elite
sports performance, but the T allele is not
associated with endurance performance.
• C allele more likely to achieve improvements in
strength, speed, power training compared to T
• T carriers should be realistic about their power
potential
• CC genotypes: be aware of Hypertension and
Left Ventricular hypertrophy
ACTN3
The ACTN3 actinin is a major structural
component of the Z line in Type II (fast) skeletal
muscles. The R allele is found more in Sprint and
Power sports people compared to the X (null)
allele.
• R allele carriers more likely to achieve
improvements in strength, speed, power training
compared to X
• X carriers should be realistic about their
strength and power potential
BDRKB2
Bradykinin is an endothelial dependent
vasodilator. The -9 SNP increases BDRKB2
expression and improves the efficiency of
muscular contraction. The +9 SNP is associated
with more thirst and fluid loss.
• -9 SNP more likely to achieve success in
endurance sport
• +9 carriers should be realistic about endurance
potential and anticipate fluid loss and
compensate during prolonged activity
ADRB2
Arg16Gly
Beta 2 Adrenergic receptors help regulate
endocrine and central nervous functions.
Adrenaline supports blood glucose levels during
prolonged exercise. The Arg SNP is better for
endurance, but may have delayed recovery after
exercise.
• Arg carriers more likely to achieve higher
VO2max and endurance success, but may need
longer recovery after exercise
• Gly carriers likely to be poorer at endurance, but
may recover quicker after exercise
• Gly carriers should monitor heart rate closely
ADRB2
Gln27Glu
Beta 2 Adrenergic receptors help regulate
endocrine and central nervous functions.
Adrenaline supports blood glucose levels during
prolonged exercise. Gln more associated with
endurance and fat burning; Glu with power and
muscle growth.
• Gln carriers more likely to achieve higher
VO2max and endurance success and better fat
burning
• Glu carriers more likely to be good at power and
strength sports and may need to vary exercise
intensities for fat burning
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Gene
Implication
Training & Nutrition Action
Genetic Variants Associated with Power and Endurance
TRHR
The Thyrotropin-releasing hormone receptor
affects metabolic rate, helps catecholamines to
mobilise fuels during exercise and is involved in
growth. The GG SNP on rs16892496 and TT on
rs7832552, are favourable for increased lean
body mass and therefore strength.
• The rare genotypes (GG - rs16892496 and TT rs7832552) are more likely to increase muscle
mass in response to training
• Other genotypes should be realistic about
power/strength potential based on information
from other genes
NRF-2
The NRF-2 protein improves respiratory capacity
and increases the rate of ATP production during
exercise. The very rare G allele is associated with
greater improvements in VO2max: around 50 to
60% better results.
• Carriers of the G allele are in a huge minority,
but are likely to have a big endurance advantage
• Other genotypes might expect more normal
VO2max improvements, depending on other gene
expressions
PPARGC1A
PPARGC1A is involved in energy homeostasis and
muscle fibre type conversion towards type I
fibres. The Ser allele is associated with lower
levels of PPARGC1A and reduced aerobic
improvements with exercise training.
• Gly carriers are more likely to maintain high
levels of energy and to be good at endurance.
• Ser carriers should be realistic about endurance
potential and should also monitor blood pressure
PPAR-alpha promotes catabolism of fatty acids,
especially during carbohydrate deprivation. G
allele is associated with type I muscle fibre
specialisation and endurance; the C allele has
been associated more with power sports.
• Be aware of sporting potential – endurance for
G alleles and power for C alleles and train
accordingly
• C allele carriers should be aware of the risk for
LV hypertrophy with training and monitor HR
VEGF
VEGF affects new blood vessel growth, impacting
on VO2max and potentially strength adaptations.
The CC genotype of the VEGF gene is associated
with higher VEGF levels and increased VO2max
levels at baseline plus a better VO2max response
to training.
• CC genotype more likely to adapt well to
endurance and power training
• GG are low VEGF producers and should be
realistic about training adaptations – may
progress more with adjustments in intensity and
nutritional circulatory support
VDR
The Vitamin D receptor is involved in bone
homeostasis, cell proliferation, immune support,
lipolysis and insulin secretion. Taq1 tt
homozygotes have shown better muscle strength,
but higher fasting glucose and insulin levels when
physical activity is low. Fok1 FF genotype
associated with greater strength and gains in
bone mineral density with exercise.
• Taq1 tt genotype more likely to gain from
strength training, but will need a range of
exercise to control glucose and insulin
ACE
ACE is a vasoconstrictor and blood pressure
regulator. The I allele is associated with lower
ACE activity: the II genotype is an endurance
profile, associated with increased muscle
efficiency. DD genotype is a power profile,
associated with greater muscle growth with
weight training.
• II genotype will gain well from endurance
training, less so from heavy strength work
• ID genotype is intermediate between power and
endurance
• DD genotype will gain better muscle growth and
strength from power training
PPARA
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Gene
Implication
Training & Nutrition Action
Genetic Variants Associated with Tendon Pathology
GDF5
GDF5 has a role to play in the development and
healing of skeletal, joint and soft tissues. The
major T allele raises the risk of sports and
training injuries, specifically Achilles tendon
pathology, and has been linked to osteoarthritis
and dislocation of the hip.
• Carriers of the T allele are at an increased risk of
tendinopathy and osteoarthritis
• Be aware of the upper limit of repetitive motion
that might trigger a tendon injury
• Incorporate resistance exercise for tendon
health into training programme
• Consider anti-inflammatory and tissue-building
nutritional strategies
COL5A1
COL5A1 codes for Type V collagen, which forms
parts of tendons and ligaments and regulates
fibril growth. The T allele increases risk of
tendonopathies, is associated with decreased
muscular range of motion, but is associated with
faster endurance running.
• Carriers of the T allele are at an increased risk of
tendinopathy
• Be aware of the upper limit of repetitive motion
that might trigger a tendon injury
• Incorporate resistance exercise for tendon
health & flexibility into training programme
• Consider anti-inflammatory and tissue-building
nutritional strategies
COL1A1
COL1A1 codes for Type I collagen, the main
fibrillar collagen found in most connective
tissues, including tendons, ligaments and
cartilage. The T allele appears to decrease the
risk for ligament injuries in sport, even though it is
a predisposing factor for osteoporosis.
• Carriers of the C allele are at a higher risk of
ligament injuries compared to T alleles
• Take care with sports that involve twisting under
force (eg. game sports)
• Train for lateral and rotational agility Consider
nutritional strategies for connective tissue
support
• T allele carriers should include bone-loading
exercise to decrease chances of osteoporosis
Genetic Variants Associated with Recovery
IL-6R
The IL-6 receptor influences IL-6 action which has
been linked to fatigue and delayed recovery
during exercise. Subjects with the C alleles may
have higher levels of IL-6, thereby increasing the
acute inflammatory effects of exercise.
• C alleles carriers are advised to increase their
recovery time between training bouts and
training sessions
• Regularly check inflammatory biomarkers
• Increase anti-inflammatory nutritional support
CRP
C-reactive protein is part of the innate immune
system and is involved in acute and chronic
inflammation. The unusual AA genotype has been
associated with lower levels of CRP and therefore
inflammation, compared to carriers of the major
G allele.
• G alleles carriers are advised to increase their
recovery time between training bouts and
training sessions
• Regularly check inflammatory biomarkers to
modulate exercise volume and intensity
• Increase anti-inflammatory nutritional support
IL6
IL-6 (a cytokine) stimulates an immune response
to trauma such as strenuous exercise and excess
cytokine release has been implicated in
overtraining syndrome. The C allele has been
linked to an increased IL-6 and CRP response to
exercise.
• C alleles carriers are advised to increase their
recovery time between training bouts and
training sessions
• Regularly check inflammatory biomarkers to
modulate exercise volume and intensity
• Increase anti-inflammatory nutritional support
SOD2 is a potent free radical scavenger within the
cell, especially the mitochondria, without which
cellular damage may occur. C allele is associated
with high levels of oxidative stress and long-term
disease if antioxidant consumption is insufficient.
• C alleles carriers are advised to moderate their
training volume and intensity to limit oxidative
stress
• Increase anti-oxidant nutritional support
SOD2
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Gene
Implication
Training & Nutrition Action
Genetic Variants Associated with Recovery
TNF
TNF is a pro-inflammatory cytokine that
stimulates the acute phase inflammatory
reaction. The A allele is associated with increased
TNF and CRP levels and potentially greater
fatigue and slower recovery.
• A alleles carriers are advised to increase their
recovery time between training bouts and
training sessions
• Increase anti-inflammatory nutritional support
Glossary of Terms
• Allele - different forms of the same gene that may affect the genotype.
• Base pair – in the DNA double helix structure, bases from one DNA strand join with bases from the other: A and T form
pairs and C and G form pairs.
• Bases – a gene is a string of bases, like letters that make up a long word: A, C, G & T.
• Chromosomes - packages of DNA that are visible during cell division. They are easily studied and useful for gene mapping.
• Codon - sequences of three nucleotides, which specify which amino acid will be added next during protein synthesis. •
• Cytokines – messengers of the immune system.
• Delta Efficiency (of muscular contraction) – the amount of energy required to perform a certain muscular contraction
activity.
• DNA - the genetic material in the fertilised egg (mostly in the nucleus and some in the mitochondria). With cell division,
DNA is replicated to each new cell.
• Gene – a sequence of DNA that confers a particular biological expression (phenotype).
• Genome - sum total of all genes in an individual or population.
• Genotype - specific DNA sequence for a certain gene.
• Heterozygous - different alleles on each chromosome for a particular gene.
• Homozygous - same alleles on both chromosomes for a particular gene.
• Locus – region of a chromosome associated with a particular physical trait.
• Nucleotides - molecules that when joined together, make up the structural units of RNA and DNA.
• Phenotype - specific physical trait as a result of the genotype.
• Polymorphism – see SNP.
• Pressor response - increasing cardiac output as a result of sympathetic nervous system innervation. SNP (single-nucleotide
polymorphism) - variants that change one letter (a base) of the genetic sequence.
• Transcription Factor - a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of
genetic information from DNA to RNA.
• Under-Performance Syndrome – another name for Over-Training Syndrome.
• VO2max – maximum aerobic capacity.
• vVO2max – predicted running speed at VO2max intensity.
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