Is there a functional relationship between the polymorphisms genotypes of the mitochondrial biogenesis pathway and mtdna copy numbers in high-level physical capacity men? A pilot study

Abstract

INTRODUCTION: Mitochondrion is the cellular organelle that produces energy for the organism generating adenosine triphosphate (ATP) using O2 and nutrients. Physical capacity levels are thus directly related with mitochondrial activity (1). Mitochondrial DNA (mtDNA) copy number is proportional to the mtDNA volume in a cell, and can be used as a marker of mitochondrial function (2). Several polymorphisms in the genes of the cellular mitochondrial regulation pathway are already known to be related with the elite athlete status and physical capacity (3,4). Nevertheless, to date, there is few information about the functional relationship between these polymorphisms and the physiological mechanisms leading to an improvement of the physical capacity. The aim of this study was to evaluate the possible functional relationship between mitochondrial pathway genes and the mitochondrial activity in men with high cardiorespiratory fitness level. METHODS: We measured the leukocyte mtDNA copy number in 38 healthy men aged between 18-45 with a VO2max above 55 ml.kg1.min-1 using a Mitochondrial to Nuclear DNA Ratio kit. The analysed singles nucleotide polymorphisms (SNPs) of the biogenesis pathway were: Peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PPARGC1A) G482S (rs8192678); Nuclear Respiratory Factor 1 (NRF1) A>G (rs6949152) and Nuclear Respiratory Factor 2 (NRF2) A>C (rs12594956); Mitochondrial Transcription Factor-A (TFAM) S12T (rs1937); Peroxisome Proliferator-Activated Receptor-delta (PPARD) A>G (rs2267668)). For statistical analyses, we used the SPSS for Windows software version 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS: None of the analyses presented significant association between the different genotypes of the selected polymorphisms and the mtDNA copy numbers (all P>0,071). CONCLUSION: Our results in this pilot study presented important inter-individual variability for mtDNA copy number, even in the groups of subjects presenting the same genotypes in each SNP. This could explain the lack of signification for the studied associations. Furthermore, our results did not show the significant relationship generally found by other authors between the genotypes of the polymorphisms of the biogenesis pathway genes and markers of physical capacity like VO2max (all P>0,062). In the future, we plan to increase the number of subjects, in order to try to reduce the variability of our results.