THE ASSOCIATION OF GENE POLYMORPHISMS WITH ATHLETE STATUS IN UKRAINIANS

Athletic performance is a polygenic trait influenced by both environmental and genetic factors. Objective: to investigate individually and in combination the association of common gene polymorphisms with athlete status in Ukrainians. Methods: A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110 power-orientated athletes) and 326 controls were genotyped for ACE I/D, HIF1A Pro582Ser, NOS3 –786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B Ala203Pro gene polymorphisms, most of which were previously reported to be associated with athlete status or related intermediate phenotypes in different populations. Results: Power-oriented athletes exhibited an increased frequency of the HIF1A Ser (16.1 vs. 9.420P = 0.034) and NOS3 T alleles (78.3 vs. 66.220P = 0.0019) in comparison with controls. Additionally, we found that the frequency of the PPARG Ala allele was significantly higher in power-oriented athletes compared with the endurance-oriented athletes (24.7 vs. 13.520P = 0.0076). Next, we determined the total genotype score (TGS, from the accumulated combination of the three polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score) in athletes and controls. The mean TGS was significantly higher in power-oriented athletes (39.1 ± 2.3 vs. 32.6 ± 1.5; P = 0.0142) than in controls. Conclusions: We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles were associated with power athlete status in Ukrainians

The PPARA gene polymorphism in team sports athletes

Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates lipid and glucose metabolism. Accumulating evidence suggests that the intron 7 C allele of the PPARA gene rs4253778 G/C polymorphism has an advantage for power-oriented athletes, presumably due to the hypertrophic effects on skeletal muscle and increase in glucose utilization in response to anaerobic exercise. The G allele, however, is said to be favorable for the endurance-oriented athletes. The metabolic demands of team sports involve aerobic and anaerobic energy pathways, as a result of the intermittent physical activity. The aim of the present study was to investigate the association between the PPARA gene polymorphism and team-sport athletic status. A total of 665 Russian athletes from 14 team sports and 1,706 controls were involved in the case-control study. We found that the frequency of the PPARA C allele was significantly higher in athletes compared to controls (20.5 vs. 16.4%, P = 0.0009), suggesting that anaerobic rather than aerobic metabolism may be crucial to the game performance in team sports. This means that our study indicates the association between the PPARA gene G/C polymorphism and team-sport athletic status. Although more replication studies are needed, the preliminary data suggest an opportunity to use the analysis of PPARA polymorphism, along with other gene variations and standard phenotypic assessment in team sports selection

Genetic variation, protein composition and potential influences on tendon properties in humans

Sequence variations in genes that code for proteins involved in homeostatic processes within tendons may influence tendon mechanical properties. Since variants of the four genes COL5A1, TNC, MMP3 and GDF5 have been implicated in the aetiopathogenesis of tendinopathies, which is ultimately characterised by abnormal structural and regulatory processes, sequence variations in these four genes may also influence how the tendon functions mechanically, even in the absence of tendinopathy. For example, two reports of association between variation in the COL5A1 gene and measures of flexibility complement reported associations between genotype and incidence of tendinopathy. Non-genetic factors such as age, body mass and physical activity status influence risk of tendon injury and physical performance potential independently from genomics, and also in gene-environment interactions. However, these non-genetic factors are often not considered in genetic association studies, probably due to their retrospective nature. Further research examining COL5A1, TNC, MMP3 and GDF5, as well as other genes that may influence the maintenance of tendon homeostasis such as COL1A1 which regulates the production of collagen type 1, the most abundant structural component of tendon is encouraged. Establishing the genetic basis of tendon properties in asymptomatic populations may advance understanding of some aspects relevant to physical performance and of the aetiology of tendinopathies. To improve understanding, accurate and reproducible assessments of tendon properties are required. However, no valid and reliable assessments of tendon properties, such as those involving in vivo ultrasound imaging techniques, have yet been applied to genetic association studies in humans

The -9/+9 polymorphism of the bradykinin receptor beta 2 gene and athlete status: A study involving two European cohorts.

Background: Previous studies concerning the relevance of the BDKRB2 gene polymorphisms revealed that the absence (–9 allele) of a 9 base pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, as well as endurance athletic performance. Aim: The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of east-European athletes. Therefore, we examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication study of Russian athletes. Methods: Three hundred and two Polish athletes and 684 unrelated sedentary controls as well as 822 Russian athletes and 507 unrelated sedentary volunteers were recruited for this study. All samples were genotyped for the -9/+9 polymorphism within exon 1 of the BDKRB2 gene using a polymerase chain reaction (PCR). Significance was assessed by χ2 analysis with Bonferroni\u27s correction for multiple testing. Results: We have not found any statistical difference in the -9/+9 genotype and allele frequencies in two groups of athletes divided into four subgroups, i.e. endurance, sprint-endurance, sprint-strength and strength athletes, when compared with controls. There weren\u27t any significant differences found in allele frequencies (P = 0.477) and genotype distribution (P = 0.278) in the initial and replication studies. Conclusion: No association was found between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of east- European athlete

FABP2 Ala54Thr Polymorphism and Post-Training Changes of Body Composition and Biochemical Parameters in Caucasian Women

The functional FABP2 Ala54Thr polymorphism (rs1799883) is strongly associated with lipid and carbohydrate metabolism, although the function of its potential modifying effect on training-induced changes in obesity-related parameters is still unknown. The aim of the present study was to investigate the influence of the Ala54Thr polymorphism on post-training changes of selected body mass and body composition measurements, as well as with biochemical parameters of energy metabolism. Accordingly, alleles and genotypes distribution in a group of 168 young, nonobese Caucasian women measured for chosen body composition parameters, lipid profile, and glucose levels before and after the completion of a 12-week aerobic training program were studied. Although the obtained results showed changes in body mass, BMI, FM, %FM, FFM, TBW, HDL-C, and glucose levels during the training program, none of the examined parameters changed significantly across the FABP2 genotypes. Instead, we found a main effect of genotype on BMI (p = 0.033), with carriers of the Thr54 allele having a higher BMI during the whole study period compared with the Ala54 carriers. We confirm that the FABP2 Ala54Thr polymorphism may help identify women at risk for overweight and obesity. However, we did not notice evidence of an interaction between physical activity and the Ala54Thr polymorphism on the examined parameters

PPARGC1A gene polymorphism is associated with exercise-induced fat loss

Obesity is a widespread problem within modern society, serving to increase the risk of cardiovascular, metabolic, and neurodegenerative disorders. Peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator 1 α (PGC1α) play a key role in the regulation of cellular energy metabolism and is implicated in the pathology of these diseases. This study examined the association between polymorphisms of the PPARG and PPARGC1A genes and individual variability in weight loss in response to physical activity intervention. 39 obese Ukrainian women (44.4 ± 7.5 years, BMI > 30.0 kg/m2) undertook a 3-month fitness program whilst following a hypocaloric diet (~ 1500 cal). Anthropometric and biochemical measurements took place before and after the program. Single nucleotide polymorphisms within or near PPARG (n = 94) and PPARGC1A (n = 138) were identified and expression of PPARG mRNA was measured via reverse transcription and amplification. The association between DNA polymorphisms and exercise-induced weight loss, initial body mass, biochemistry and PPARG expression was determined using one-way analysis of variance (ANOVA). The present intervention induced significant fat loss in all participants (total fat: 40.3 ± 5.3 vs 36.4 ± 5.7%; P < 0.00001). Only one polymorphism (rs17650401 C/T) within the PPARGC1A gene was found to be associated with fat loss efficiency after correction for multiple testing, with T allele carriers showing the greatest reduction in body fat percentage (2.5-fold; P = 0.00013) compared to non-carriers. PPARGC1A (rs17650401) is associated with fat loss efficiency of the fitness program in obese women. Further studies are warranted to test whether this variation is associated with fat oxidation

Association of gene polymorphisms with body weight changes in prediabetic patients

Recent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146. Knowledge of the association between these single nucleotide polymorphisms (SNPs) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders. From 327 patients, a subgroup of 81 prediabetic female patients (48.7 ± 14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146 polymorphisms were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR = 1.46, p = 0.05 and OR = 2.47, p = 0.006, respectively). PPARG CC homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05). We have shown that the obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency. Furthermore, we confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk. [Abstract copyright: © 2022. The Author(s).

Genetic profile of sports climbing athletes from three different ethnicities

This study aimed to investigate the ACTN3 R577X, ACE I/D, CKM rs8111989, and TRHR rs7832552 genotypes in climbers and controls in three ethnicities. The study consisted of 258 climbers (Japanese, n = 100; Polish, n = 128; Russian, n = 30) and 1151 controls (Japanese: n = 332, Polish: n = 635, Russian: n = 184). Genotyping results were analyzed using the TaqMan approach in Japanese and Polish subjects and HumanOmni1-Quad Bead Chips in Russian subjects. There were no significant differences in ACTN3 R577X and ACE I/D polymorphism distribution between climbers and controls in any ethnic cohort or model. The frequencies of the C allele in the CKM polymorphism and the T allele in the TRHR polymorphism were higher in climbers than in controls only in the Russian cohort (p = 0.045 and p = 0.039, respectively). The results of the meta-analysis on three cohorts showed that the frequency of XX + RX genotypes in the ACTN3 R577X polymorphism was significantly higher in climbers than that in the controls (p = 0.01). The X allele of the ACTN3 R577X polymorphism was associated with sport climbing status, as assessed using a meta-analysis of climbers across three different ethnicities

Skeletal muscle hypertrophy rewires glucose metabolism: an experimental investigation and systematic review

BACKGROUND: Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. METHODS: We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. RESULTS: The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-13C6]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8). CONCLUSIONS: Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis