The rs12594956 polymorphism in the NRF-2 gene is associated with top-level Spanish athlete's performance status

Objectives: To determine the association between the nuclear respiratory factor 2 (NRF-2) polymorphisms and elite athletic performance. Design: We compared the genotype and allele frequencies of the NRF-2 A/C (rs12594956), NRF-2 A/G (rs7181866), and NRF-2 C/T (rs8031031) polymorphisms between world-class endurance athletes (n=89), elite power-oriented athletes (n=38), and non-athletic controls (n=110) of the same Caucasian (Spanish) origin. Methods: Genomic DNA was extracted from peripheral EDTA-treated, anti-coagulated blood using a standard protocol. Genotyping was performed using polymerase chain reaction (PCR). Results: The frequency of the AA genotype of the NRF-2 A/C (rs12594956) polymorphism was significantly higher in endurance athletes compared with power athletes (p<0.01) and controls (p<0.01) (48% vs. 13% and 21%, respectively). The likelihood of having the AA (rs12594956) genotype was higher in elite endurance athletes compared with controls [odds ratio (OR): 3.536, 95% confidence interval (CI): 1.903-6.571] and elite power athletes (OR: 6.170, 95%CI: 2.206-17.253). Conclusions: Our results suggest that the NRF-2 A/C polymorphism might belong to a growing group of polymorphisms associated with endurance performance at the elite level. However, it is important to replicate these findings in other groups of elite athletes using larger sample sizes.