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

Abstract

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.

Similar skeletal muscle angiogenic and mitochondrial signalling following 8 weeks of endurance exercise in mice: discontinuous versus continuous training

“…There was, however, no increase in protein expression for VEGFR1 in the same muscle during the same time period (Milkiewicz et al 2003). Recently, Ahmetov et al (2009) examined VEGFR2 allele frequencies in 471 elite Russian endurance athletes and 603 control subjects. The investigators reported that the VEGFR2 472Gln allele was prevalent in various types of endurance athletes, such as swimmers and road cyclists, relative to control subjects (Ahmetov et al 2009).…”

“…Recently, Ahmetov et al (2009) examined VEGFR2 allele frequencies in 471 elite Russian endurance athletes and 603 control subjects. The investigators reported that the VEGFR2 472Gln allele was prevalent in various types of endurance athletes, such as swimmers and road cyclists, relative to control subjects (Ahmetov et al 2009). The authors suggested that this phenotype in skeletal muscle may cause an increased affinity for VEGF binding.…”

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

“…Consequently, gene variations could be considered as molecular determinants maintaining the expression of the slow or fast myosin heavy chain isoforms of adult skeletal muscle. Indeed, several polymorphisms of genes involved in the calcineurin/NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia/angiogenesis and circulatory homeostasis are reported to be candidate genetic markers for determination of muscle fibre composition (Zhang et al 2003, Ahmetov et al 2006, 2008, 2009 a , b ; Vincent et al 2007). One possible explanation for the relationship between α‐actinin‐3 deficiency ( ACTN3 XX genotype) and slow‐twitch muscle fibre phenotype observed previously, and confirmed in the present study, could be evidence that α‐actinins interact with signalling proteins, such as calcineurin (reviewed by Berman & North, 2010).…”

Current Progress in Sports Genomics

“…Studies have reported that the His472-Gln polymorphism influences the efficiency of VEGF binding to VEGFR2 [169]. In a study of 182 endurance-oriented Russian athletes, the significantly higher frequency of the VEGFR2 472Gln allele compared to controls was reported [170]. Furthermore, the 472Gln allele was also shown to be significantly associated with a higher proportion of type I fibers of m. vastus lateralis (determined by immunohistochemistry) in both athletes (all-round speed skaters, n ¼ 23; age 20.4 AE 0.5 years) and physically active men (n ¼ 45; age 23.5 AE 0.4 years), and with a greater VO 2max in female rowers [170].…”