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

Abstract

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.

Endothelial nitric oxide synthase g894t (rs1799983) gene polymorphism in polish athletes

“…There were no differences in the G894T allele frequencies in athletes stratified by the level of competitiveness (elite versus sub-elite) regardless of the athletes' status (power, "mixed" and endurance). Ahmetov et al [38] suggested that the difference in allelic frequencies between athletes within the same event category (for example strength/power sports), but with different levels of achievements may be explained by selection pressure. Specifically, the athletes possessing a "desired" allele or its combination are more likely to become elite.…”

Gene Polymorphisms and Fiber-Type Composition of Human Skeletal Muscle

“…Specifically, for men with high numbers (≥9) of endurance alleles (n = 26) compared with those with low numbers (≤8) of endurance alleles (n = 19), there was a greater number of slow-twitch fibers in the vastus lateralis (56.1% ± 1.8% vs. 43.8% ± 2.2%, p = 1.0 × 10 -4 ; these results remained statistically significant after correction for multiple testing) and a higher proportion of area occupied by those fibers (50.0% vs. 41.8%, p = .033; Ahmetov, Williams, et al, 2009).…”

“…We recently found that the frequency of the VEGFR2 472Gln allele was significantly higher in endurance-oriented Russian athletes than in controls. The 472Gln allele was also shown to be significantly related to a higher proportion of Type I fibers of vastus lateralis (determined by immunohistochemistry) in both athletes (all-round speed skaters, n = 23, age 20.4 ± 0.5 years) and physically active men (n = 45, age 23.5 ± 0.4 years; Ahmetov, Hakimullina, et al 2009). …”

“…It was shown that ACE deletion (D) allele (of the Alu I/D polymorphism) is associated with high serum and tissue ACE activity, Ahmetov, Hakimullina, et al, 2009 hypertension, Type 2 diabetes, obesity, coronary heart disease, and myocardial infarction (Kennon, Petrie, Small, & Connell, 1999;Rieder & Nickerson, 2000;Strazzullo et al, 2003). An excess of the ACE insertion (I) allele was found in endurance-oriented athletes compared with controls in several studies (reviewed in , indicating that the ACE I allele is favorable for aerobic performance.…”

“…Therefore, large sample sizes are needed to detect associations with single polymorphisms, and various combinatorial approaches should be used where the phenotypic variance associated with several genetic variants can be assessed simultaneously. We recently quantified the association between a combination of genotypes and fiber composition of vastus lateralis (determined by immunohistochemistry) in 45 healthy men (age 23.5 ± 0.4 years; Ahmetov, Williams, et al, 2009). For that analysis, we used 10 polymorphisms of genes involved in the calcineurin-NFAT pathway (PPP3R1 promoter 5I/5D, NFATC4 Gly160Ala), mitochondrial biogenesis (PPARGC1A Gly482Ser, PPARGC1B Ala203Pro, TFAM Ser12Thr), glucose and lipid metabolism (PPARA rs4253778 G/C, PPARD rs2016520 T/C), hypoxia/angiogenesis (VEGFA rs2010963 G/C), and thermogenesis (UCP2 Ala55Val, UCP3 rs1800849 C/T).…”