Are calcineurin genes associated with endurance phenotype traits?

Polymorphisms in calcineurin genes are candidates to explain individual variations in endurance phenotype traits owing to the pivotal role that the calcineurin signaling pathway plays in the regulation of important cardiac and skeletal muscle phenotypes such as slow myosin heavy chain expression, skeletal muscle oxidative capacity or cardiac hypertrophy. We studied the possible association of 55 polymorphisms in the calcineurin gene isoforms PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2 with both baseline levels and responsiveness to a 18-week endurance training program of maximal oxygen uptake (VO(2)max) and running economy (RE) in healthy young Chinese men [n = 102; mean (SD) age 19 +/- 1 years] of Han origin. We used two-way (genotype, training) ANOVA for repeated measures to compare baseline and trainability of VO(2)max and RE among genotypes of the aforementioned polymorphisms. We found a significant association between (a) baseline VO(2)max and the rs2850965 and rs3804423 polymorphisms in the PPP3CA gene; (b) training responsiveness of VO(2)max and both the rs3804358 polymorphism (PPP3CA) and the rs4671887 polymorphism (PPP3R1); and (c) training responsiveness of RE and rs3739723 (PPP3R2). Though more research is needed, our findings suggest that polymorphisms in the calcineurin genes might be among the numerous potential genetic variant candidates that, together with other factors (e.g., environment, complex genetics interactions), can help explaining human variations in endurance exercise phenotype traits.