ArticlePDF Available

Genetics-based performance talent research: Polymorphisms as predictors of endurance performance

Authors:

Abstract

N/A.
A preview of the PDF is not available
... Furthermore, it is estimated that approximately 30,000 genes and approximately 10 million single nucleotide polymorphisms (SNPs) may be related in some way to physical performance (Schoenfelder 2010), with heritability estimates of genetic traits related to the athletic performance phenotype varying between 20 and 75% (MacArthur and North 2005;Schoenfelder 2010). Although estimates suggest the possibility of a large number of genes contributing to physical performance, until 2005 approximately 170 genetic variations (165 autosomal and 5 X-linked) have been identified improving athletic performance when inherited (Ostrander et al. 2009). ...
... Furthermore, it is estimated that approximately 30,000 genes and approximately 10 million single nucleotide polymorphisms (SNPs) may be related in some way to physical performance (Schoenfelder 2010), with heritability estimates of genetic traits related to the athletic performance phenotype varying between 20 and 75% (MacArthur and North 2005;Schoenfelder 2010). Although estimates suggest the possibility of a large number of genes contributing to physical performance, until 2005 approximately 170 genetic variations (165 autosomal and 5 X-linked) have been identified improving athletic performance when inherited (Ostrander et al. 2009). ...
Article
Full-text available
Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. The results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.
... Furthermore, it is estimated that approximately 30,000 genes and approximately 10 million single nucleotide polymorphisms (SNPs) may be related in some way to physical performance (Schoenfelder 2010), with heritability estimates of genetic traits related to the athletic performance phenotype varying between 20 and 75% (MacArthur and North 2005;Schoenfelder 2010). Although estimates suggest the possibility of a large number of genes contributing to physical performance, until 2005 approximately 170 genetic variations (165 autosomal and 5 X-linked) have been identified improving athletic performance when inherited (Ostrander et al. 2009). ...
... Furthermore, it is estimated that approximately 30,000 genes and approximately 10 million single nucleotide polymorphisms (SNPs) may be related in some way to physical performance (Schoenfelder 2010), with heritability estimates of genetic traits related to the athletic performance phenotype varying between 20 and 75% (MacArthur and North 2005;Schoenfelder 2010). Although estimates suggest the possibility of a large number of genes contributing to physical performance, until 2005 approximately 170 genetic variations (165 autosomal and 5 X-linked) have been identified improving athletic performance when inherited (Ostrander et al. 2009). ...
Article
Full-text available
Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. Results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.
... It is estimated that approximately 30,000 genes and approximately 10 million SNPs may be related in some way to physical performance, with heritability estimates varying between 20 and 75% [70] . Although several candidate genes have been proposed to explain individual differences in human endurance phenotypic traits, particularly those involved in energy metabolism or cardiovascular function [10,13] , muscle efficiency has been less studied in the scientific literature than these traits [10] , and it is also a critical factor determining endurance performance. In this context, although cardiorespiratory fitness was not tested in our work by the conventional methods (V O 2max , V O 2 R, HR max , HRR and LT, among others), the fitness of the athletes in terms of muscle performance was established here through biochemical parameters and complies with previous reports [3,72] . ...
Article
Full-text available
Background/aims: As diet can affect an individual's genes and these can affect response to supplementation, we aimed to investigate the influence of erythropoietin (EPO T→G) and α-actinin-3 (ACTN3 R577X) polymorphisms on plasma lipid peroxidation, hemogram and biochemical dosages of creatine kinase, aspartate aminotransferase, alanine aminotransferase and C-reactive protein (including high-sensitivity C-reactive protein) of runners (n = 123) before and after 14 days of 400 mg pequi oil supplementation, a natural carotenoid-rich oil, after races under closely comparable conditions. Methods/results: Blood samples were taken immediately after racing to perform the tests. Before pequi oil supplementation, EPO polymorphism influenced erythrogram and plateletgram results, suggesting an aerobic advantage for the TG genotype and a disadvantage for the GG genotype as regards possible microvascular complications, while no association was found for ACTN3 polymorphism with endurance performance. Both polymorphisms influenced the runners' response to pequi oil: significant responses were observed for the EPO TT genotype in erythrocyte, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration values, and for the TT and TG genotypes in red blood cell distribution width values. Significant differences were also observed in the plateletgram for the TT and TG genotypes. ACTN3 mainly influenced aspartate aminotransferase and creatine kinase values: heterozygotes had a significant reduction in aspartate aminotransferase values and homozygous individuals (XX) in creatine kinase values after pequi oil supplementation. Conclusion: These results emphasize the importance of studying nutrigenomic effects on athletes' performance.
... Over the course of evolution, families pass on their genetic coding from one generation to the next and certain characteristics of genes are added, subtracted, and altered over time. Schoenfelder reported [1] that the heritability of athletic status was approximately 66% in a twin pair study, but he did not state whether it was influenced by single or multiple genes. Over the last two decades, many sports science studies have been conducted to investigate the relationship of genetics and elite athletic performance, and the association of genetic characteristics and their impacts on training and exercise. ...
Article
Full-text available
Angiotensin-converting enzyme (ACE) is a component of the circulating renin–angiotensin system, which influences circulatory homeostasis through the degradation of vasodilator kinins and the generation of vasopressor angiotensin II. Various phenotypic characteristics such as diseases and human performances could be associated with genetic polymorphisms within the ACE gene. To date, one of the most well-studied genetic polymorphisms that has been shown to be associated with athletic performance is that of the ACE gene. Previous studies investigating the influences of polymorphisms and various phenotypic characteristics have produced inconsistent findings due to inter-ethnic variations in the distribution of the different ACE alleles. For example, some studies showed that the I allele was associated with fatigue resistance in skeletal muscle and endurance performance while the D allele had been associated with power or sprint performance. Nevertheless, controversy still exists regarding the above conclusion as related studies reported that the I allele was associated with a better power or sprint performance rather than with athletic endurance abilities. This article discusses the inter-ethnic variations of the distribution of the different ACE alleles in several ethnic groups such as in European, African, American, and Asian populations. Additionally, the influences of the ACE ID polymorphism on human physical fitness performances in European and other populations are discussed.
Article
Full-text available
Endurance performance is a complex phenotype subject to the influence of both environmental and genetic factors. Although the last decade has seen a variety of specific genetic factors proposed, many in metabolic pathways, each is likely to make a limited contribution to an ‘elite’ phenotype: it seems more likely that such status depends on the simultaneous presence of multiple such variants. The aim of the study was to investigate individually and in combination the association of common metabolic gene polymorphisms with endurance athlete status, the proportion of slow-twitch muscle fibers and maximal oxygen consumption. A total of 1,423 Russian athletes and 1,132 controls were genotyped for 15 gene polymorphisms, of which most were previously reported to be associated with athlete status or related intermediate phenotypes. Muscle fiber composition of m. vastus lateralis in 45 healthy men was determined by immunohistochemistry. Maximal oxygen consumption of 50 male rowers of national competitive standard was determined during an incremental test to exhaustion on a rowing ergometer. Ten ‘endurance alleles’ (NFATC4 Gly160, PPARA rs4253778 G, PPARD rs2016520 C, PPARGC1A Gly482, PPARGC1B 203Pro, PPP3R1 promoter 5I, TFAM 12Thr, UCP2 55Val, UCP3 rs1800849 T and VEGFA rs2010963 C) were first identified showing discrete associations with elite endurance athlete status. Next, to assess the combined impact of all 10 gene polymorphisms, all athletes were classified according to the number of ‘endurance’ alleles they possessed. The proportion of subjects with a high (≥9) number of ‘endurance’ alleles was greater in the best endurance athletes compared with controls (85.7 vs. 37.8%, P=7.6×10−6). The number of ‘endurance’ alleles was shown to be positively correlated (r=0.50; P=4.0×10−4) with the proportion of fatigue-resistant slow-twitch fibers, and with maximal oxygen consumption (r=0.46; P=7.0×10−4). These data suggest that the likelihood of becoming an elite endurance athlete depends on the carriage of a high number of endurance-related alleles.
Article
Full-text available
Hypoxia-inducible factor-1alpha (HIF1A) is a transcription factor regulating several genes in response to hypoxic stimuli. HIF1A target genes code for proteins involved in oxygen transport, glycolytic enzymes, and glucose transporters. We investigated whether single-nucleotide polymorphisms and haplotypes in the HIF1A gene are associated with endurance performance in the Genathlete cohort, which includes 316 Caucasian male elite endurance athletes (EEA) with a maximal oxygen uptake of 79.0+/-3.5 ml.kg(-1).min(-1) (mean+/-SD) and 304 Caucasian male sedentary controls with a maximal oxygen uptake of 40.1+/-7.0 ml.kg(-1).min(-1). Six single-nucleotide polymorphisms (rs1951795, rs11158358, rs2301113, rs11549465, rs115494657, rs17099207) were genotyped with the TaqMan system. We found a nominal significant tendency for a difference between the two groups for HIF1A Pro582Ser (rs11549465) genotype distributions (Pchi2=0.017). Homozygotes of the Pro genotype were slightly more frequent in athletes than in controls (84 vs. 75%). Compared with Ser carriers, the odds ratio (OR) of being an EEA in Pro/Pro homozygotes was 1.77 [95% confidence interval (CI): 1.18-2.67, P=0.006] compared with the other genotypes. A common HIF1A haplotype (frequency: 15%), including the rs11549465 Pro allele and the minor A allele of rs17099207 in the 3' flanking region of the gene, showed a significant association with EEA status (OR: 2.37, 95% CI: 1.21-4.66, P=0.012), whereas the most prevalent haplotype (frequency: 59%) comprising the rs11549465 Pro allele and the major G allele of rs1709920 showed no association with EEA status (OR: 0.93, 95% CI: 0.58-1.50, P=0.769). We found preliminary evidence that the HIF1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men.
Article
Full-text available
The American Society for Nutrition hosted a symposium entitled Nutrients and Epigenetic Regulation of Gene Expression at the Experimental Biology meeting on April 20, 2009, in New Orleans, LA. The symposium was cochaired by Emily Ho from Oregon State University and the Linus Pauling Institute, and Janos Zempleni from the University of Nebraska at Lincoln. The goal of this symposium was to highlight the interactions among nutrients, epigenetics, and disease susceptibility. The symposium featured 4 speakers, each presenting novel insights into mechanisms by which nutrients participate in gene regulation. Janos Zempleni elucidated mechanisms by which the covalent binding of biotin to histones represses transposable elements, thereby enhancing genome stability. Emily Ho shared valuable insights into bioactive food compounds that inhibit histone deacetylases. James Kirkland from the University of Guelph in Canada talked about a niacin-dependent poly(ADP-ribosylation) of histones, an epigenetic mark that is not currently being given full consideration in nutrition. Patrick Stover from Cornell University described the interrelationships among 1-carbon metabolism, DNA methylation, gene silencing, and their influence in the etiology of folate-related pathologies. All 4 presentations were videotaped and can be viewed online (www.nutrition.org).
Article
Full-text available
Significant data confirming the influence of genes on human physical performance and elite athlete status have been accumulated in recent years. Research of gene variants that may explain differences in physical capabilities and training-induced effects between subjects is widely carried out. In this review, the findings of genetic studies investigating DNA polymorphisms and their association with elite athlete status and training responses are reported. A literature search revealed that at least 36 genetic markers (located within 20 autosomal genes, mitochondrial DNA and Y-chromosome) are linked to elite athlete status and 39 genetic markers (located within 19 genes and mitochondrial DNA) may explain, in part, an interindividual variability of physical performance characteristics in response to endurance/strength training. Although more replication studies are needed, the preliminary data suggest an opportunity to use some of these genetic markers in an individually tailored prescription of lifestyle/exercise for health and sports performance.
Article
A low maximal oxygen consumption (VO2max) is a strong risk factor for premature mortality. Supervised endurance exercise training increases VO2max with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts VO2max training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous VO2max response. Two independent preintervention RNA expression data sets were generated (n=41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in VO2max ("predictor" genes). The HERITAGE Family Study (n=473) was used for genotyping. We discovered a 29-RNA signature that predicted VO2max training response on a continuous scale; these genes contained approximately 6 new single-nucleotide polymorphisms associated with gains in VO2max in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., "reciprocal" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in VO2max, corresponding to approximately 50% of the estimated genetic variance for VO2max. In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. VO2max responses to endurance training can be predicted by measuring a approximately 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
Article
Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared with normal tissue, and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.
Article
Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium-calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.
Article
This update of the human gene map for physical performance and health-related fitness phenotypes covers the research advances reported in 2006 and 2007. The genes and markers with evidence of association or linkage with a performance or a fitness phenotype in sedentary or active people, in responses to acute exercise, or for training-induced adaptations are positioned on the map of all autosomes and sex chromosomes. Negative studies are reviewed, but a gene or a locus must be supported by at least one positive study before being inserted on the map. A brief discussion on the nature of the evidence and on what to look for in assessing human genetic studies of relevance to fitness and performance is offered in the introduction, followed by a review of all studies published in 2006 and 2007. The findings from these new studies are added to the appropriate tables that are designed to serve as the cumulative summary of all publications with positive genetic associations available to date for a given phenotype and study design. The fitness and performance map now includes 214 autosomal gene entries and quantitative trait loci plus seven others on the X chromosome. Moreover, there are 18 mitochondrial genes that have been shown to influence fitness and performance phenotypes. Thus,the map is growing in complexity. Although the map is exhaustive for currently published accounts of genes and exercise associations and linkages, there are undoubtedly many more gene-exercise interaction effects that have not even been considered thus far. Finally, it should be appreciated that most studies reported to date are based on small sample sizes and cannot therefore provide definitive evidence that DNA sequence variants in a given gene are reliably associated with human variation in fitness and performance traits.
Article
Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD. Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification. Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups. The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.
Article
Historically, the achievement of maximal oxygen uptake (VO2max) has been based on objective criteria such as a leveling off of oxygen uptake with an increase in work rate, high levels of lactic acid in the blood in the minutes following the exercise test, elevated respiratory exchange ratio, and achievement of some percentage of an age-adjusted estimate of maximal heart rate. These criteria are reviewed relative to their history, the degree to which they have been achieved in published research, and how investigators and reviewers follow them in current practice. The majority of the criteria were based on discontinuous protocols, often carried out over several days. Questions are raised about the applicability of these criteria to modern continuous graded exercise test protocols, and our lack of consistency in the terminology we use relative to the measurement of maximal oxygen uptake.