Cellular Aspects of Muscle Specialization Demonstrate Genotype – Phenotype Interaction Effects in Athletes

Abstract

Introduction Gene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes. Methods Muscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes ( n = 29), power athletes ( n = 17), and untrained non-athletes ( n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi 2 tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P -values below 0.05 were considered statistically significant. Results The athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers. Discussion ACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports.

Muscle Fiber Type Transitions with Exercise Training: Shifting Perspectives

“…Finally, it is also important to point out that genetic predisposition, in part, can explain some of the observed interindividual differences in fiber type make-up [ 42 , 43 ]. In this regard, the ACTN3 R577X genotype has been associated with muscle fiber type composition, where individuals harboring the RR genotype possess more type IIx fibers compared to those with the XX genotype [ 44 ].…”

Sarcoplasmic Hypertrophy in Skeletal Muscle: A Scientific “Unicorn” or Resistance Training Adaptation?

“…In this regard, two of the studies mentioned above which have observed features of sarcoplasmic hypertrophy have been in well-trained bodybuilders ( Macdougall et al, 1982 ; Meijer et al, 2015 ), and this population generally trains with higher volumes. Conversely, there are features of myofibril packing in power athletes ( Meijer et al, 2015 ; Fluck et al, 2019 ), and this population generally trains with higher loads and lower volumes. The two aforementioned studies from our laboratory also support this model ( Haun et al, 2019b ; Vann et al, 2020a ), and it is notable that a reduction in myofilament packing density via sarcoplasmic hypertrophy may also promote certain training adaptations such as increased muscle fiber shortening velocity ( Metzger and Moss, 1987 ).…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…A proper mitochondrial turnover is crucial in muscle adaptation to exercise given that abnormal proteostasis leads to loss of contractile proteins in aged muscles [127,128]. However, despite controlled physical activity, complete muscle restoration is impossible due to unavoidable oxidative deterioration of fast glycolytic fibers and enhanced expression of age-related genes insensitive to exercise benefit [129,130].…”