Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes.

The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes' status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups - weightlifters (87), powerlifters (60), throwers (14); by elite status - 'elite' (104), 'sub-elite' (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the 'preferable genotype' for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls.

[SIGNALING PATHWAYS INVOLVED IN THE REGULATION OF PROTEIN METABOLISM IN SKELETAL MUSCLE].

The ability of muscle cells to respond to certain signaling molecules depends on the presence of specific proteins-receptors, ion channels and transporters, which create a system of metabolic inputs. All cells in the human body have a transmembrane signaling system that allows to get information from extracellular stimuli such as hormones, neurotransmitters, proteins, peptides, derivatives of amino acids and fat acids, sensor molecules. The results of researches published in the last two years, which expand knowledge of action of various factors on protein metabolism in skeletal muscles are presented in the review. The main attention is turned to the discovery and expansion of signaling pathways involved in the regulation of protein metabolism in skeletal muscle in different functional states of the person.

[THE ROLE OF microRNAs IN THE REGULATION OF MUSCLE METABOLTSM].

MicroRNAs, class of the small RNA containing approximately 22 nucleotides take part in regulation of metabolism of skeletal muscles as enzymes, hormones and transcription factors. They are able to regulate the intensity of the translation process through complementary. interaction with mRNA. The review presents the results of studies published in the last two years, which increase the knowledge of the effects of microRNAs on the key stages of protein synthesis in skeletal muscle. The main attention is paid to achievements which open and specify a microRNA role in regulation of the signaling pathways that coordinate intracellular metabolism of skeletal muscles at different finctionni onneiilinnc nf then

[Molecular mechanisms of skeletal muscle hypertrophy].

Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

[Participation AMPK in the regulation of skeletal muscles metabolism].

Enzyme AMPK is a part of the family of serine/threonine specific protein kinases. AMPK plays important role in the transfer extracellular signals through phosphorylation of multiple substrates in different metabolic reactions of skeletal muscles. AMPK is geterotrimetric complex, consisting of the catalytic subunit (AMPKalpha) and two regulatory subunits (AMPKbeta and AMPKgamma), which are encoded by seven different high-homologous genes (alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3). AMPK regulates skeletal muscle metabolism through phosphorylation of various enzymes such as carbohydrate, lipid and protein metabolism, as well as factors of transcription and initiation. The AMPK expression occurs in response to a changing metabolic requests muscle cells and it leads to increased energy metabolism. The data of recent studies suggest the important role of AMPK in the regulation of intracellular metabolism and point to the need to study the molecular mechanisms involved in the regulation of gene expression in skeletal muscle.

The ACTN3 R577X polymorphism in Russian endurance athletes.

OBJECTIVE: The functional 577R allele of the alpha-actinin-3 (ACTN3) gene has been reported to be associated with elite power athlete status, while the nonfunctional 577XX genotype (predicts an alpha-actinin-3 deficient phenotype) has been hypothesised as providing some sort of advantage for endurance athletes. In the present study, the distribution of ACTN3 genotypes and alleles in Russian endurance-oriented athletes were examined and association between ACTN3 genotypes and the competition results of rowers were sought. METHODS: 456 Russian endurance-oriented athletes of regional or national competitive standard were involved in the study. ACTN3 genotype and allele frequencies were compared with 1211 controls. The data from the Russian Cup Rowing Tournament were used to search for possible association between the ACTN3 genotype and the long-distance (approximately 6 km) rowing results of 54 athletes. DNA was extracted from mouthwash samples. Genotyping for the R577X variant was performed by PCR and restriction enzyme digestion. RESULTS: The frequencies of the ACTN3 577XX genotype (5.7% vs 14.5%; p<0.0001) and 577X allele (33.2% vs 39.0%; p = 0.0025) were significantly lower in endurance-oriented athletes compared with the controls, and none of the highly elite athletes had the 577XX genotype. Furthermore, male rowers with ACTN3 577RR genotype showed better results (1339 (11) s) in long-distance rowing than carriers of 577RX (1386 (12) s) or 577XX (1402 (10) s) genotypes (p = 0.016). CONCLUSION: Our data show that the ACTN3 577X allele is under-represented in Russian endurance athletes and is associated with the rowers' competition results.

[Association of regulatory genes polymorphisms with aerobic and anaerobic performance of athletes].

The aim of study was to investigate an allelic distribution of PPARA (G/C polymorphism), PPARG (Pro/Ala), PPARD (+294T/C) and PGCIA (Gly482Ser) genes in rowers (n=205) and controls (n=659), and to find correlation between genotypes and physiological parameters. Genotyping was performed by restriction fragment length polymorphism analysis. Physiological parameters were evaluated by PM 3 Rower Ergometer and MetaMax 3B Gas Analyzer. The frequencies ofPPARA G (90.1% vs. 83.6%) and PPARG Ala (23.1% vs. 16.2%) alleles in elite athletes, and of PPARD C (19.1% vs. 10.5%) and PGC1A Gly (75.4% vs. 66.5%) alleles in sub-elite athletes were significantly higher than in controls. Moreover, PPARA G (when oxygen pulse was measured) and PGC 1A Gly (when maximal aerobic power and anaerobic threshold (%) of VO2max were measured) alleles were associated with high values of aerobic performance. Thus, PPARA G, PPARG Ala, PPARD C and PGCIA Gly alleles can be considered as genetic markers associated with enhanced physical performance.

[The association of gene polymorphisms with the muscle fiber type composition].

Muscle fiber composition of m. vastus lateralis has significant individual variability mainly depending on genetic factors. Present study shows analysis of association between polymorphisms of three muscle performance-related genes and muscle fiber type composition in 48 young healthy men. DNA was obtained from mouthwash samples by alkaline extraction. Polymorphism determination of PPARalpha, ACE and ACTN3 genes was performed using polymerase chain raction. Muscle fiber typing from m. vastus lateralis was performed using immunohistochemistry method. We found an association of increased frequency of intron 7 G allele of PPARalpha gene (93.9% vs 60.0%) and D allele of ACE gene (68.8% vs 34.4%) in the group with the highest proportion of slow-twitch fibers (56-70%) compared to the group with the lowest proportion (25-43%). Thus, PPARalpha and ACE genes can be considered as potential candidate genes for muscle fiber type determination.

[Androgen regulation of the level of tissue-specific proteins in skeletal muscles during physical exercise]. / Androgennaia reguliatsiia soderzhaniia tkanespetsificheskikh belkov v skeletnykh myshtsakh pri fizicheskikh nagruzkakh.

Administration of testosterone after exercises led to suppression of the hormone production during the anabolic phase within 72-120 hrs of muscles adaptation to physical loading. Content of the androgen receptors was also altered. The supercompensatory phase in content of proteins (myoglobin and aspartate aminotransferase as index) was absent due to an impairing effect of testosterone on muscle adaptation. These data suggest that administration of testosterone could not serve as an adequate model of a body androgenization which was observed in anabolic phase of muscle adaptation to physical exercises.

[Aspartate aminotransferase metabolism in muscles during physical exercise]. / Metabolizm aspartataminotransferazy v myshtsakh pri fizicheskoi nagruzkakh.

It is established that the concentration of cytosolic aspartate aminotransferase decreases the first day after intensive physical exercises due to the intensification of the degradation processes, the decrease in the synthesis rate and the enzyme entry into the blood vessel. The enzyme content is normalized by the 24th hour of rest and then the supercompensatory phase takes place: the enzyme biosynthesis increases and its degradation decreases to a greater extent.