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 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.

Genes and Athletic Performance: An Update.

Humans vary in their ability to achieve success in sports, and this variability mostly depends on genetic factors. The main goal of this work was to review the current progress in the understanding of genetic determinism of athlete status and to describe some novel and important DNA polymorphisms that may underlie differences in the potential to be an elite athlete. In the past 19 years, at least 155 genetic markers (located within almost all chromosomes and mtDNA) were found to be linked to elite athlete status (93 endurance-related genetic markers and 62 power/strength-related genetic markers). Importantly, 41 markers were identified within the last 2 years by performing genome-wide association studies (GWASs) of African-American, Jamaican, Japanese, and Russian athletes, indicating that GWASs represent a promising and productive way to study sports-related phenotypes. Of note, 31 genetic markers have shown positive associations with athlete status in at least 2 studies and 12 of them in 3 or more studies. Conversely, the significance of 29 markers was not replicated in at least 1 study, raising the possibility that several findings might be false-positive. Future research, including multicentre GWASs and whole-genome sequencing in large cohorts of athletes with further validation and replication, will substantially contribute to the discovery of large numbers of the causal genetic variants (mutations and DNA polymorphisms) that would partly explain the heritability of athlete status and related phenotypes.

Current Progress in Sports Genomics.

Understanding the genetic architecture of athletic performance is an important step in the development of methods for talent identification in sport. Research concerned with molecular predictors has highlighted a number of potentially important DNA polymorphisms contributing to predisposition to success in certain types of sport. This review summarizes the evidence and mechanistic insights on the associations between DNA polymorphisms and athletic performance. A literature search (period: 1997-2014) revealed that at least 120 genetic markers are linked to elite athlete status (77 endurance-related genetic markers and 43 power/strength-related genetic markers). Notably, 11 (9%) of these genetic markers (endurance markers: ACE I, ACTN3 577X, PPARA rs4253778 G, PPARGC1A Gly482; power/strength markers: ACE D, ACTN3 Arg577, AMPD1 Gln12, HIF1A 582Ser, MTHFR rs1801131 C, NOS3 rs2070744 T, PPARG 12Ala) have shown positive associations with athlete status in three or more studies, and six markers (CREM rs1531550 A, DMD rs939787 T, GALNT13 rs10196189 G, NFIA-AS1 rs1572312 C, RBFOX1 rs7191721 G, TSHR rs7144481 C) were identified after performing genome-wide association studies (GWAS) of African-American, Jamaican, Japanese, and Russian athletes. On the other hand, the significance of 29 (24%) markers was not replicated in at least one study. Future research including multicenter GWAS, whole-genome sequencing, epigenetic, transcriptomic, proteomic, and metabolomic profiling and performing meta-analyses in large cohorts of athletes is needed before these findings can be extended to practice in sport.

A common polymorphism of the MCT1 gene and athletic performance.

PURPOSE: In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79). METHODS: Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer. RESULTS: Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005). CONCLUSIONS: MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.