Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates gene expression in response to hypoxia, and has been associated with athletic performance. The aims of this study were 1) to determine the frequency distribution of HIF1A Pro582Ser (rs11549465) polymorphism among 155 Israeli athletes (sprinters and endurance athletes) and 240 healthy controls and 2) to analyze the influence of the interaction between HIF1A Pro582Ser and ACTN3 R577X (rs1815739) genotypes on sprint performance. There were no differences across the HIF1A genotype and allele frequencies among endurance athletes, sprinters and controls. Similarly, no differences were found between the subgroups of top-level and national-level endurance athletes, or between top-level and national-level sprinters.Conversely, interaction effects were found between HIF1A Pro582Ser and ACTN3 R577X polymorphisms and sprinters. The proportion of HIF1A Pro/Pro + ACTN3 R/R genotypes was significantly higher in sprinters than in endurance athletes and healthy controls (P=0.002). In addition, the odds ratio for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being a sprinter was 2.25 (95% confidence interval 1.24-4.1), and for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being an endurance athlete was 0.5 (95% confidence interval 0.2-1.24). We conclude that HIF1A Pro582Ser polymorphism by itself is not critical in determining sprint performance. However, sprinter performance is determined by the interaction between the wild-type HIF1A Pro/Pro genotype and ACTN3 RR genotype.3

The Association of Gene Polymorphisms With Athlete Status in Ukrainians

“…We also identified a polygenic profile (by the use of combination of the HIF1A , NOS3 and PPARG polymorphisms) of power-oriented athletes that allowed us, at least partly, to distinguish power-oriented athletes from controls. These polymorphisms have already been associated with power athlete status and/or power-related phenotypes in other studies [3, 4, 9, 13–15, 20], so our data replicate those previous findings.…”

“…The frequency of the HIF1A Ser allele was significantly higher in Russian weightlifters and wrestlers than in controls and increased with their levels of achievement [3, 14]. These results were replicated in a cohort of Polish power-orientated athletes [9], but not in Israeli sprinters [13]. Furthermore, the Ser allele was significantly associated with an increased proportion of fast-twitch muscle fibres in m. vastus lateralis of all-round speed skaters [3].…”

Current Progress in Sports Genomics

“…highly elite (25.0%)). These results were replicated in three cohorts of 158 Polish power-orientated athletes [218], 208 Russian power-oriented athletes (122 weightlifters and 86 wrestlers) [219], and 110 Ukrainian power-oriented athletes [220], but not in 81 Israeli sprinters [221]. Furthermore, the 582Ser allele was significantly associated with an increased proportion of fast-twitch muscle fibers in m. vastus lateralis of all-round speed skaters [217].…”

ACTN3 and AMPD1 Polymorphism and Genotype Combinations in Bulgarian Athletes Performing Wingate Test

“…However, a handful of athletes with the RX genotype have shown excellent results in power/sprint events [22]. Recently, the research has been focused on the influence of ACTN3 R-power allele dominant (RR + RX) model alone [22,24] or in combination with other genes [16,26].…”