The A-allele of the FTO Gene rs9939609 Polymorphism Is Associated With Decreased Proportion of Slow Oxidative Muscle Fibers and Over-represented in Heavier Athletes.

Guilherme, JPLF, Egorova, ES, Semenova, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Ospanova, EA, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Govorun, VM, Generozov, EV, Ahmetov, II, and Lancha Junior, AH. The A-allele of the FTO gene rs9939609 polymorphism is associated with decreased proportion of slow oxidative muscle fibers and over-represented in heavier athletes. J Strength Cond Res 33(3): 691-700, 2019-The purpose of this study was to explore the frequency of the FTO T > A (rs9939609) polymorphism in elite athletes from 2 cohorts (Brazil and Russia), as well as to find a relationship between FTO genotypes and muscle fiber composition. A total of 677 athletes and 652 nonathletes were evaluated in the Brazilian cohort, whereas a total of 920 athletes and 754 nonathletes were evaluated in the Russian cohort. It was found a trend for a lower frequency of A/A genotype in long-distance athletes compared with nonathletes (odds ratio [OR]: 0.65; p = 0.054). By contrast, it was found an increased frequency of the A-allele in Russian power athletes. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a Russian power athlete compared with matched nonathletes (OR: 1.45; p = 0.002). Different from that observed in combat sports athletes of lighter weight categories, the A-allele was also over-represented in combat sports athletes of heavier weight categories. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a combat sports athlete of heavier weight categories compared with nonathletes (OR: 1.79; p = 0.018). Regarding the muscle fibers, we found that carriers of the A/A genotype had less slow-twitch muscle fibers than T-allele carriers (p = 0.029). In conclusion, the A/A genotype of the FTO T > A polymorphism is under-represented in athletes more reliant on a lean phenotype and associated with decreased proportion of slow-twitch muscle fibers, while is over-represented in strength and heavier athletes.

Three DNA Polymorphisms Previously Identified as Markers for Handgrip Strength Are Associated With Strength in Weightlifters and Muscle Fiber Hypertrophy.

Grishina, EE, Zmijewski, P, Semenova, EA, Cieszczyk, P, Huminska-Lisowska, K, Michalowska-Sawczyn, M, Maculewicz, E, Crewther, B, Orysiak, J, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Bondareva, EA, Erskine, RM, Generozov, EV, and Ahmetov, II. Three DNA polymorphisms previously identified as markers for handgrip strength are associated with strength in weightlifters and muscle fiber hypertrophy. J Strength Cond Res 33(10): 2602-2607, 2019-Muscle strength is a highly heritable trait. So far, 196 single nucleotide polymorphisms (SNPs) associated with handgrip strength have been identified in 3 genome-wide association studies. The aim of our study was to validate the association of 35 SNPs with strength of elite Russian weightlifters and replicate the study in Polish weightlifters. Genotyping was performed using micro-array analysis or real-time polymerase chain reaction. We found that the rs12055409 G-allele near the MLN gene (p = 0.004), the rs4626333 G-allele near the ZNF608 gene (p = 0.0338), and the rs2273555 A-allele in the GBF1 gene (p = 0.0099) were associated with greater competition results (total lifts in snatch and clean and jerk adjusted for sex and weight) in 53 elite Russian weightlifters. In the replication study of 76 sub-elite Polish weightlifters, rs4626333 GG homozygotes demonstrated greater competition results (p = 0.0155) and relative muscle mass (p = 0.046), adjusted for sex, weight, and age, compared with carriers of the A-allele. In the following studies, we tested the hypotheses that these SNPs would be associated with skeletal muscle hypertrophy and handgrip strength. We found that the number of strength-associated alleles was positively associated with fast-twitch muscle fiber cross-sectional area in the independent cohort of 20 male power athletes (p = 0.021) and with handgrip strength in 87 physically active individuals (p = 0.015). In conclusion, by replicating previous findings in 4 independent studies, we demonstrate that the rs12055409 G-, rs4626333 G-, and rs2273555 A-alleles are associated with higher levels of strength, muscle mass, and muscle fiber size.

A Genome-Wide Association Study of Sprint Performance in Elite Youth Football Players.

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leonska-Duniec, A, Pajak, B, Chycki, J, Moska, W, Lulinska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cieszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.

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

Muscle fibre type is a heritable trait and can partly predict athletic success. It has been proposed that polymorphisms of genes involved in the regulation of muscle fibre characteristics may predispose the muscle precursor cells of a given individual to be predominantly fast or slow. In the present study, we examined the association between 15 candidate gene polymorphisms and muscle fibre type composition of the vastus lateralis muscle in 55 physically active, healthy men. We found that rs11091046 C allele carriers of the angiotensin II type 2 receptor gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory homeostasis) had a significantly higher percentage of slow-twitch fibres than A allele carriers [54.2 (11.1) versus 45.2 (10.2)%; P = 0.003]. These data indicate that 15.2% of the variation in muscle fibre composition of the vastus lateralis muscle can be explained by the AGTR2 genotype. Next, we investigated the frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control subjects. The frequency of the AGTR2 C allele was significantly higher in male and female endurance athletes compared with power athletes (males, 62.7 versus 51.7%, P = 0.0038; females, 56.6 versus 48.1%, P = 0.0169) and control subjects (males, 62.7 versus 51.0%, P = 0.0006; elite female athletes, 65.1 versus 55.2%, P = 0.0488). Furthermore, the frequency of the AGTR2 A allele was significantly over-represented in female power athletes (51.9%) in comparison to control subjects (44.8%, P = 0.0069). We also found that relative maximal oxygen consumption was significantly greater in male endurance athletes with the AGTR2 C allele compared with AGTR2 A allele carriers [n = 28; 62.3 (4.4) versus 57.4 (6.0) ml min(-1) kg(-1); P = 0.0197]. Taken together, these results demonstrate that the AGTR2 gene C allele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance, while the A allele is associated with a higher percentage of fast-twitch fibres and power-oriented disciplines.

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)%; = 0.215; P = 0.049) in the overall muscle biopsy group, and with PRD of all athletes ( = 0.24, P = 0.010), indicating thatACTN3 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.

The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes.

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.

Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes.

Vascular endothelial growth factor receptor 2 (VEGFR2) is essential to induce the full spectrum of VEGF angiogenic responses to aerobic training. In the present study, we examined the impact of the functional His472Gln polymorphism of the VEGFR2 gene on elite athlete status, endurance performance and muscle fibre type composition. Four hundred and seventy-one Russian athletes were prospectively stratified into four groups according to event duration, distance and type of activity, covering a spectrum from the more endurance-oriented to the more power-oriented. VEGFR2 genotype and allele frequencies were compared to 603 controls. To examine the association between VEGFR2 genotype and fibre type composition, vastus lateralis muscle biopsies were obtained from 45 physically active healthy men and 23 all-round speed skaters. In addition, 76 competitive rowers performed incremental endurance exercise to allow analysis of genotype associations with exercise responses. We found that the frequency of the VEGFR2 472Gln allele was significantly higher in endurance-oriented athletes compared to controls (36.8 vs. 27.4%, P = 0.0006). Relative VO(2max) was significantly greater in the VEGFR2 472Gln allele carriers compared with the His/His homozygotes of the sub-elite female rower group only. Genotype-specific differences were found for the proportion of slow-twitch fibres in both athletes and controls, which was approximately 10.1 and approximately 7.4% higher in the His/Gln and Gln/Gln genotypes than in the His/His genotype group, respectively. In conclusion, we have shown for the first time that variation in the VEGFR2 gene is associated with elite athlete status, endurance performance of female rowers and muscle fibre type composition.

PPARalpha gene variation and physical performance in Russian athletes.

Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates genes responsible for skeletal and heart muscle fatty acid oxidation. Previous studies have shown that the PPARalpha 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). PPARalpha 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 PPARalpha 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, PPARalpha intron 7 G/C polymorphism was associated with physical performance in Russian athletes, and this may be explained, in part, by the association between PPARalpha genotype and muscle fiber type composition.