Purpose: Polymorphisms in calcineurin genes are candidates to explain individual variations in endurance sports performance owing to the pivotal role that the calcineurin signaling pathway plays in the regulation of important cardiac and skeletal muscle phenotypes.
Methods: We compared genotypic/allelic frequencies in 55 single nucleotide polymorphisms (SNP) of the five genes (PPP3CA, PPP3CB, PPP3CC, PPP3R1, and PPP3R2) encoding the calcineurin protein subunits between 123 elite runners (cases, n = 61 women) and 125 healthy nonathletes (controls, n = 56 women) from the same ethnic background (Han Chinese) and used the dual-luciferase reporter assay to analyze the functional significance of the associated SNP.
Results: The C allele of the PPP3CA rs3804358 polymorphism was overrepresented in athletes (17%) compared with controls (8%) (P = 0.003), whereas the T allele of the PPP3CB rs3763679 polymorphism was underrepresented in athletes (23%) compared with controls (37%) (P = 0.001). The luciferase reporter constructs containing C allele of the rs3804358 and rs3763679 polymorphisms produced significantly greater luciferase activity than that of the G or T alleles, respectively. However, the results on the two aforementioned polymorphisms were not corroborated in a Caucasian (Spanish) cohort of male elite endurance athletes (n = 100) and nonathletic male controls (n = 175).
Conclusions: Although there are large differences between ethnicities and more research is needed, our findings suggest that intronic polymorphisms of the calcineurin genes have functional significance and show evidence of association with elite endurance performance in the northern Han Chinese population.