Beneficial Effects of Cardiomyopathy-Associated Genetic Variants on Physical Performance: A Hypothesis-Generating Scoping Review

Abstract

<b><i>Background:</i></b> Genetic variants associated with cardiomyopathies (CMPs) are prevalent in the general population. In young athletes, CMPs account for roughly a quarter of sudden cardiac death, with further unexplained clustering in specific sports. Consequently, most CMPs form a contraindication for competitive sports. We hypothesized that genetic variants might (paradoxically) improve physical performance early in life while impairing cardiac function later in life. <b><i>Methods:</i></b> Systematic PubMed search was done to investigate whether genetic variants in genes associated with CMPs could be related to beneficial performance phenotypes. <b><i>Summary:</i></b> In a limited number of studies (<i>n</i> = 6), 2,860 individuals/subjects with genetic variants were able to outperform those without said variants, as measured by running speed (∼38 m/min in heterozygous [HET] mice, <i>n</i> = 6, vs. ∼32 m/min in wild type [WT] mice, <i>n</i> = 7, <i>p</i> = 0.004) and distance (966 ± 169 km HET mice vs. 561 ± 144 km WT mice, <i>p</i> = 0.0035, <i>n</i> = 10), elite athlete status in endurance athletes (<i>n</i> = 1,672, <i>p</i> = 1.43 × 10⁻⁸), maximal oxygen uptake in elite athletes (absolute difference not provided, <i>n</i> = 32, <i>p</i> = 0.005), maximal oxygen uptake in unrelated individuals (<i>n</i> = 473, <i>p</i> = 0.0025), personal records in highly trained marathon runners (2:26:28 ± 0:06:23 min HET, <i>n</i> = 32, vs. 2:28:53 ± 0:05:50 min without polymorphism, <i>n</i> = 108, <i>p</i> = 0.020), and peripheral muscle force contraction in patients following a cardiac rehabilitation program (absolute values not provided, <i>n</i> = 260). <b><i>Key Message:</i></b> Beneficial effects in genetic variants associated with CMPs could hypothetically play a role in the selection of young athletes, consequently explaining the prevalence of such genetic variants in athletes and the general population.