No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes.

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.

Homozygosity for a premature stop codon at amino acid position 577 in the alpha-actinin-3 (ACTN3) gene leads to α-actinin-3 deficiency. This genotype is observed in approximately 18% of Caucasians. The ACTN3 R577X polymorphism has been previously associated with indicators of physical performance in several, but not all, studies. We examined the prevalence of R577X (rs1815739) and two additional haplotype tagging single nucleotide polymorphisms (htSNPs) of the ACTN3 gene (rs1791690 and rs2275998) in the Genathlete study comprising 316 male elite endurance athletes (VO2max 79.0+3.5 ml · kg(-1) · min(-1); mean +/- s) from North America, Finland, and Germany and 304 sedentary controls (VO2max 40.1+7.0 ml · kg(-1) · min(-1) matched by country of origin. The distribution of genotype and allele frequencies between the two groups was tested by Pearson chi-square and/or Fischer exact test. The prevalence of the 577X homozygote genotype was similar in endurance athletes and controls (20% and 17.5%, respectively). The resulting odds ratio for endurance performance in 577X homozygotes compared with 577R-allele carriers was 1.24 (95%CI 0.82-1.87, P = 0.3). The genotype distribution of the two htSNPs and haplotype frequencies did not differ significantly between athletes and controls. In conclusion, our findings indicate that ACTN3 R577X and other SNPs in ACTN3 are not genetic determinants of endurance performance in Caucasian males.

A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1alpha (HIF1A) gene in elite endurance athletes.

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.

Association between a beta2-adrenergic receptor polymorphism and elite endurance performance.

The Arg16Gly single nucleotide polymorphism of the human beta(2)-adrenoceptor (ADRB2) gene was evaluated in a case-control study that included 313 white male elite endurance athletes and 297 white male sedentary controls (SCs) recruited in a multicenter project from North America, Finland, and Germany. The groups were matched by country of origin. The elite endurance athletes were required to have a maximum oxygen uptake > or = 75 mL.kg(-1).min(-1) (mean [SD], 79.0 [3.5]), whereas SC subjects had to be sedentary with a measured maximum oxygen uptake < or = 50 mL.kg(-1).min(-1) (40.1 [7.0]). Polymerase chain reaction technique was used to amplify the single nucleotide polymorphism-containing region in codon 16 of the ADRB2 gene. ADRB2 genotypes were in Hardy-Weinberg equilibrium in both groups. Genotypes did not differ between countries or sports of the athletes. The chi(2) analysis for the genotype distribution showed a significant difference between the 2 cohorts (P = .030), suggesting a positive association between the tested Arg16Gly polymorphism and endurance performance. Comparing carriers vs non-carriers for the 2 alleles, an excess of Gly allele carriers was seen in the SC group (P = .009), indicating an unfavorable effect of the Gly allele with respect to the performance status. In conclusion, we found suggestive evidence that the Arg16Gly polymorphism in the gene encoding for the beta(2)-adrenergic receptor may associate with endurance performance status in white men.

Effects of short-term normobaric hypoxia on haematology, muscle phenotypes and physical performance in highly trained athletes.

This study aimed to determine the impact of short-term normobaric hypoxia on physiology and performance in highly trained athletes. Twelve (7 male and 5 female) athletes were randomly assigned into two groups and spent 8 h per night for two consecutive nights a week over 3 weeks under either short-term normobaric hypoxia (simulating 3636 m altitude, inspired O2=13%) or in normobaric normoxia in a single-blind study. Following a 3 week washout period, athletes were then exposed to the other condition. Athletes were tested for maximal oxygen consumption and time to exhaustion on an electromagnetically braked cycle ergometer before and after each treatment in addition to being tested for anaerobic performance (Wingate test) on a modified Monark cycle ergometer. Blood samples were taken throughout the experiment and vastus lateralis muscle biopsies were taken before and after each treatment. Increases in red blood cell count, haematocrit, haemoglobin, platelet number and erythropoietin concentration were observed following short-term normobaric hypoxia. Except for a modest decrease in phosphofructokinase activity following short-term normobaric hypoxia, no changes were observed in muscle enzyme activities, buffer capacity, capillary density or morphology. No performance measures were changed following short-term normobaric hypoxia or normobaric normoxia. Although short-term normobaric hypoxia exposure increased levels of a number of haematological parameters, this was not associated with improved aerobic or anaerobic performance in highly trained athletes.

Glycogen depletion of human skeletal muscle fibers in response to high-frequency electrical stimulation.

The purpose of the present study was to evaluate the pattern of change in muscular glycogen content in response to high-frequency electrical stimulation (HFES). Muscle biopsies were taken from the vastus lateralis muscle of 7 healthy young men before, 15 min after, and 30 min after electrical stimulation delivered at a 50-Hz frequency (15 s on, 45 s off) at an intensity of 100 mA. The glycogen content of type I, IIA, and IIB muscle fibres was evaluated using microphotometry of periodic acid Schiff (PAS) stained fibres. After 15 min of electrical stimulation, the glycogen content in type I, IIA, and IIB muscle fibres significantly decreased from 113 +/- 10 (mean +/- SE) to 103 +/- 10 (p < or = 0.05), 129 +/- 9 to 102 +/- 12 (p < or = 0.01), and 118 +/- 8 to 90 +/- 13 (p < or = 0.01) arbitrary relative units, respectively. No further decrement in glycogen content was observed in all three fibre types following an additional 15 min of HFES. In addition, isometric force decreased by approximately 50%, from 125.9 +/- 20.0 N to 64.2 +/- 7.7 N (p < or = 0.01), during the first 15 contractions. No further decrease in isometric force was observed following an additional 15 contractions of HFES. These results reveal that significant reductions in isometric force of knee extensor muscles and glycogen content of all human skeletal muscle fibre types in vastus lateralis muscle are observable after 15 min of neuromuscular high-frequency transcutaneous electrical stimulation.

Training profile counts for time-to-exhaustion performance.

The objective of this study was to compare the time to exhaustion (Tlim) at maximal aerobic speed (v.VO2max) in middle- and long-distance runners. Five middle-distance (MDR) and 5 long-distance (LDR) male runners, ages 28 +/- 7 years, were tested running on a treadmill, with the Université de Montréal Track Test (UMTT), on maximal velocity and on time-to-exhaustion track tests. During the laboratory test, cardiorespiratory variables (e.g., HR, .VO2max, .VCO2, .VE) were assessed. Second, running velocity at .VO2max (v.VO2max) during the UMTT was determined and HR values were recorded; also, maximal velocity on a 30-m sprint (V30) and maximal heart rate (HR max) and time to exhaustion were determined on the track. No significant difference was observed between groups during the multistage treadmill test. Significant differences were found between groups for V30 and Tlim, with MDR showing a 23% longer running time than LDR. The results of the present study demonstrated that the training profile of middle-distance and long-distance runners plays a significant role in Tlim performance when v.VO2max is obtained during a test with short-duration stages.

Treadmill and Cycle Ergometer Tests are Interchangeable to Monitor Triathletes Annual Training.

The purpose of this study was to verify the use of a single test to obtain annual training guidelines applicable to multiple modes of training. Eight triathletes (4 females, 4 males) were tested 3 times during their training year (Phase I; Phase II; Phase III) on a treadmill and cycle ergometer. Cardio-respiratory variables were calculated at standardized percentages of maximal oxygen uptake (VO2max; 50-100%). VO2max differences between tests reached 6% in every testing session (p ≤ 0.01). VO2max was stable for both tests throughout the season. The ANOVA (3 phases x 2 tests x 6 intensities) demonstrated that there was a significant difference for heart rate (HRs; p ≤ 0.05) between tests in Phase I only. However, the nonparametric sign test did not show any significant differences in any phase. These results demonstrated that triathletes could use the relationship between HR and % VO2max collected during a treadmill or a cycle ergometer test to obtain interchangeable reference HRs for monitoring their running and cycling training bouts in high volume and/or high intensity phases of their training year.