Ekaterina V. Lyubaeva

PPARα gene variation and physical performance in Russian athletes

Peroxisome proliferator-activated receptor α (PPARα) regulates genes responsible for skeletal and heart muscle fatty acid oxidation. Previous studies have shown that the PPARα intron 7 G/C polymorphism was associated with left ventricular growth in response to exercise. We speculated that GG homozygotes should be more prevalent within a group of endurance-oriented athletes, have normal fatty acid metabolism, and increased percentages of slow-twitch fibers. We have tested this hypothesis in the study of a mixed cohort of 786 Russian athletes in 13 different sporting disciplines prospectively stratified by performance (endurance-oriented athletes, power-oriented athletes and athletes with mixed endurance/power activity). PPARα intron 7 genotype and allele frequencies were compared to 1,242 controls. We found an increasing linear trend of C allele with increasing anaerobic component of physical performance (P=0.029). GG genotype frequencies in endurance-oriented and power-oriented athletes were 80.3 and 50.6%, respectively, and were significantly (P<0.0001) different compared to controls (70.0%). To examine the association between PPARα gene variant and fiber type composition, muscle biopsies from m. vastus lateralis were obtained and analyzed in 40 young men. GG homozygotes (n=25) had significantly (P=0.003) higher percentages of slow-twitch fibers (55.5±2.0 vs 38.5±2.3%) than CC homozygotes (n=4). In conclusion, PPARα intron 7 G/C polymorphism was associated with physical performance in Russian athletes, and this may be explained, in part, by the association between PPARα genotype and muscle fiber type composition.

The dependence of preferred competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters

It is generally accepted that muscle fibre composition may influence physical performance. The α‐actinin‐3 (ACTN3) gene R577X polymorphism is suspected to be one of the contributing gene variations in the determination of muscle fibre type composition and athletic status. In the present study, we examined the dependence of average preferred racing distance (PRD) on muscle fibre type composition of the vastus lateralis muscle in 34 subelite Russian speed skaters (20 men and 14 women) who competed in races of different length (500–10,000 m). We also investigated the association between the ACTN3 polymorphism and muscle fibre characteristics in 94 subjects (60 physically active healthy men and 34 speed skaters), as well as the relationship between PRD and ACTN3 genotype in 115 subelite and elite speed skaters. In addition, ACTN3 genotype and allele frequencies of the 115 speed skaters were compared with 1301 control subjects. The ACTN3 XX genotype frequency was significantly lower in sprinters (n = 39) compared with control subjects (2.6 versus 14.5%; P = 0.034). We observed a positive relationship between PRD and the proportion of slow‐twitch muscle fibres that was close to linear, but better fitted a logarithmic curve (r = 0.593, P < 0.0005). The ACTN3 R577X polymorphism was associated with muscle fibre composition (slow‐twitch fibres: RR genotype, 51.7 (12.8)%; RX, 57.4 (13.2)%; XX 61.5 (16.3)%; ρ= 0.215; P = 0.049) in the overall muscle biopsy group, and with PRD of all athletes (ρ= 0.24, P = 0.010), indicating that ACTN3 XX genotype carriers exhibit a higher proportion of slow‐twitch fibres and prefer to skate long‐distance races. However, the majority of the association between muscle fibre type and PRD was independent of ACTN3 genotype. In conclusion, the ACTN3 R577X polymorphism is associated with preferred racing distance in speed skaters and muscle fibre type composition. Thus, it is probably partly via associations with fibre type that the R577X polymorphism contributes to a small but perhaps important component of the ability to perform at a high level in speed skating.

Effect of HIF1A gene polymorphism on human muscle performance

Allele distribution of hypoxia-inducible factor gene (HIF1A; Pro582Ser polymorphism) was studied in power-oriented athletes and controls practicing no athletics; genotype relationships with muscle fiber composition were studied in speed skaters. Genotyping was carried out by PCR. The composition of muscle fibers was evaluated by the immunohistochemical analysis of m. vastus lateralis. The incidence of HIF1A Ser allele was significantly higher in weight-lifters than in controls (17.9 vs. 8.5%; p=0.001) and increased with athletic skill improvement. A relationship between HIF1A Ser allele and predominance of fast-twitch muscle fibers was shown (Pro/Ser 46.2 (13.8)%, Pro/Pro 31.4 (8.2)%; p=0.007). Hence, HIF1A Pro582Ser polymorphism is associated with muscle activity in humans.

PPARG Gene polymorphism and locomotor activity in humans.

The distribution of PPARG gene allele frequencies (Pro/Ala polymorphism) was studied in sportsmen specialized in speed and force athletics. A relationship between genotypes and human muscle transverse section area was evaluated. The PPARG Ala allele was significantly more incident in athletes than in controls, the incidence increasing with higher athletic qualification. A hypertrophic effect of PPARG Ala allele on muscle fibers was detected. Hence, the PPARG Pro12Ala polymorphism is associated with human motor activity.

AGTR2 gene polymorphism is associated with muscle fibre composition, athletic status and aerobic performance

What is the central question of this study? Variations in genes are considered to be molecular determinants maintaining the expression of the slow or fast myosin heavy chains of adult skeletal muscle. The role of polymorphisms of candidate genes involved in skeletal muscle development, energy homeostasis and thyroid and calcium metabolism in the determination of muscle fibre type has not previously been reported. What is the main finding and its importance? We show that the AGTR2 rs11091046 C allele is associated with an increased proportion of slow‐twitch muscle fibres, endurance athlete status and aerobic performance. Such findings have important implications for our understanding of muscle function in both health and disease.