A Genome-Wide Association Study of Sprint Performance in Elite Youth Football Players.

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leonska-Duniec, A, Pajak, B, Chycki, J, Moska, W, Lulinska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cieszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.

The VEGFA gene and anterior cruciate ligament rupture risk in the Caucasian population.

The aim of the present study was to analyse VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with susceptibility to anterior cruciate ligament rupture (ACLR) in a Polish population. The study included 412 physically active Caucasian participants. The study group consisted of 222 individuals with surgically diagnosed primary ACLR qualified for ligament reconstruction (ACLR group). The control group consisted of 190 apparently healthy participants without any history of ACLR (CON group). Three polymorphisms within the VEGFA (rs699947, rs1570360, and rs2010963) gene were chosen for investigation due to their significance in the angiogenesis signalling pathway and previous associations with risk of ACLRs. Both single-locus and haplotype-based analyses were conducted. No significant differences in the allele and genotype frequency distributions were noted for the rs699947 and rs1570360 polymorphisms. In contrast, rs2010963 was associated with risk of ACLR in the codominant (p=0.047) and recessive model (p=0.017). In the latter, the CC genotype was overrepresented among individuals with ACL rupture (23.4% vs 14.2%, OR=1.85 [1.11-3.08]). Two VEGFA haplotypes were associated with ACLR under the additive (global score=11.39, p=0.022) and dominant model (global score=11.61, p=0.020). The [C;G;G] haplotype was underrepresented in the ACLR group (52.2% vs. 60.3%), whereas the [C;G;C] haplotype was overrepresented (2.9% vs 0.5%). The results obtained suggest a potential correlation between the VEGFA rs2010963 polymorphism and ACLR risk, suggesting that harbouring this specific C allele may be an unfavourable risk factor for a knee injury in Caucasian participants from Poland.

Are IL1B, IL6 and IL6R Gene Variants Associated with Anterior Cruciate Ligament Rupture Susceptibility?

Cytokines, such as interleukins, are crucial in regulating critical cell signaling pathways as well as being major contributors to inflammatory response and are upregulated during ligament and tendon injuries. The genes encoding key interleukins, such as IL1B and IL6 as well as interleukin receptor IL6R, were chosen as candidate genes for association with soft tissue injuries. The aim of the case-control study was to verify the hypothesis that sequence variants rs1143627, rs16944, rs1800795, rs2228145 in the IL1B, IL6 and IL6R genes are associated with ACL rupture susceptibility in a Polish population. Among four analyzed SNPs, the rs1800795 IL6 gene polymorphism was found to be the only one significantly associated with ACL rupture (p = 0.010, p = 0.022, p = 0.004 for codominant, recessive and overdominant models, respectively; odds ratio = 1.74, 95% CI 1.08-2.81, sex adjusted p = 0.032 for recessive model). With reference to the other analyzed polymorphisms, we failed to show significant differences in the genotype and allele frequencies for IL6R rs2228145as well as IL1B rs16944 and rs1143627 (analyzed alone or in haplotype combination) between the ACL rupture group and the healthy control group among Polish participants. Due to the nature of case-control studies, the results of this study need to be confirmed in independent studies with larger sample sizes.

Are MMP3, MMP8 and TIMP2 gene variants associated with anterior cruciate ligament rupture susceptibility?

OBJECTIVES: Anterior cruciate ligament rupture (ACLR) is a common and severe knee injury which typically occurs as a result of sports participation, primarily via a non-contact mechanism. A number of extrinsic and intrinsic risk factors, including genetics, have been identified thus far. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) play a crucial role in extracellular matrix remodeling of ligaments and therefore the genes encoding MMPs and TIMPs are plausible candidates for investigation with ACL rupture risk. DESIGN: A case-control genetic association study was conducted on 229 (158 male) individuals with surgically diagnosed primary ACLR, ruptured through non-contact mechanisms and 192 (107 male) apparently healthy participants (CON) without any history of ACLR. All participants were physically active, unrelated, self-reported Caucasians. METHODS: All participants were genotyped for four single nucleotide polymorphisms (SNP): MMP3 (rs591058C/T, rs679620 G/A), MMP8 (rs11225395C/T), and TIMP2 (rs4789932 G/A) using standard PCR assays. Gene-gene interactions were inferred. Single-locus association analysis was conducted using the Chi-square test. SNP-SNP interaction effects were analysed using multifactor dimensionality reduction (MDR) method. RESULTS: Genotype frequencies did not significantly differ between cases and controls, however, the MMP3 rs679620 G and rs591058C alleles were significantly overrepresented in cases compared to controls (p=0.021, OR=1.38, 95% CI: 1.05-1.81). CONCLUSIONS: These results support the hypothesis that genetic variation within MMP3 contributes to inter-individual susceptibility to non-contact ACLR. However, these results need to be explored further in larger, independent sample sets.

Are TNC gene variants associated with anterior cruciate ligament rupture susceptibility?

OBJECTIVES: To investigate the role of inter-individual variations in a particular glycoprotein, TNC, and its potential contribution to anterior cruciate ligament (ACL) injury susceptibility in Polish Caucasian participants. ACL rupture is one of the most prevalent and severe knee injury that predominantly occurs during sports participation, primarily via a non-contact mechanism. Several polymorphisms in genes encoding glycoproteins either independently or as allelic combinations, modulate the risk of musculoskeletal soft tissue injuries. Specifically, the TNC rs1330363 (C>T), rs2104772 (T>A) and rs13321 (G>C) variants, independently or in haplotype combinations, were analysed in this context. DESIGN: Case-control genetic association study. METHODS: A group of 421 physically active, unrelated participants were recruited where 229 individuals with surgically diagnosed primary ACL rupture and 192 apparently healthy participants without any history of ACL injuries. Participants were genotyped for the above variants. RESULTS: Genotype and allele frequencies of TNC variants did not differ between cases and controls. Haplotype analysis revealed no association between TNC and predisposition to ACL rupture. CONCLUSIONS: Our analyses did not reveal a significant association between these TNC variants and risk of ACL rupture in Polish Caucasian participants.

ADIPOQ polymorphisms are associated with changes in obesity-related traits in response to aerobic training programme in women.

Among genetic variants of the ADIPOQ gene +276 G>T (rs1501299) and -11377 G>C (rs266729) are the most frequently investigated polymorphisms which were described in the context of genetic conditioning for a predisposition to obesity. However, the information of polymorphisms' potential modifying effect on obesity-related traits achieved through training procedures are still unknown. DNA was extracted from buccal cells donated by the 201 participants and genotyping was carried out using real-time PCR. The genotype distribution was examined in a group of women measured for chosen traits before and after the completion of a 12-week training programme. Our results suggest that the ADIPOQ genotypes analyzed individually or in combination can modulate training-induced body mass measurements changes: after the training programme, carriers of rs1501299 T allele and rs266729 C allele were characterized by a greater reduction in fat mass percentage (FM), fat mass, and body mass. Moreover, the ADIPOQ polymorphisms were associated with changes in lipid profile in response to training. Additionally, we showed three main effects of genotypes for the FM, LDL-C (rs266729), and TBW (rs1501299). Our study indicate that the both polymorphisms are associated with changes in obesity-related traits in response to 12-week aerobic training programme in Caucasian women. From this evidence, it could be concluded that rs1501299 G and rs266728 G variants may be considered as disadvantageous factor in the context of training-induced effects on body mass traits.

The polymorphisms of the PPARD gene modify post-training body mass and biochemical parameter changes in women.

In this study we examined the genotype distribution of the PPARD rs2267668, rs2016520, and rs1053049 alleles in a group of women, before and after the completion of a 12-week training program. There were two significant genotype × training interactions resulting in decreases of total cholesterol (Chol) through training in rs2267668 G allele carriers and significant increases of triglyceride (TGL) levels in rs2267668 AA homozygotes. Carriers of rs2016520 PPARD C allele exhibited a significant decrease in Chol through training with an accompanying decrease in TGL. There was also overrepresentation of PPARD rs1053049 TT homozygotes in the group with higher post-training TGL levels. Moreover (rs2267668/rs2016520/rs1053049) G/C/T haplotype displayed smaller post-training body mass decrease, suggesting that harboring this specific G/C/T haplotype is unfavorable for achieving the desired training-induced body mass changes. On the other hand, the G/C/C haplotype was significantly associated with post-training increase in fat free mass (FFM) and with lower levels of Chol as well as TGL as observed in the blood of the participants in response to applied training. This observation constitutes the second important finding of the study, implying that when specific training-induced biochemical changes are taken into account, some individuals may benefit from carrying the G/C/C haplotype.

C60 Fullerenes Diminish Muscle Fatigue in Rats Comparable to N-acetylcysteine or ß-Alanine.

The aim of this study is to detect the effects of C60 fullerenes, which possess pronounced antioxidant properties, in comparison with the actions of the known exogenous antioxidants N-acetylcysteine (NAC) and ß-Alanine in terms of exercise tolerance and contractile property changes of the m. triceps surae (TS) during development of the muscle fatigue in rats. The electrical stimulation of the TS muscle during four 30 min series in control rats led to total reduction of the muscle contraction force. Furthermore, the effects of prior intraperitoneal (i.p.) or oral C60FAS application and preliminary i.p. injection of NAC or ß-Alanine on muscle contraction force under fatigue development conditions is studied. In contrast to control rats, animals with C60FAS, NAC, or ß-Alanine administration could maintain a constant level of muscle effort over five stimulation series. The accumulation of secondary products and changes in antioxidant levels in the muscle tissues were also determined after the fatigue tests. The increased levels of lactic acid, thiobarbituric acid reactive substances and H2O2 after stimulation were statistically significant with respect to intact muscles. In the working muscle, there was a significant (p < 0.05) increase in the activity of endogenous antioxidants: reduced glutathione, catalase, glutathione peroxidase, and superoxide dismutase. Treated animal groups showed a decrease in endogenous antioxidant activity relative to the fatigue-induced animals (P < 0.05). Oral C60FAS administration clearly demonstrated an action on skeletal muscle fatigue development similar to the effects of i.p. injections of the exogenous antioxidants NAC or ß-Alanine. This creates opportunities to oral use of C60FAS as a potential therapeutic agent. Due to the membranotropic activity of C60 fullerenes, non-toxic C60FAS has a more pronounced effect on the prooxidant-antioxidant homeostasis of muscle tissues in rats.

Interactions between COL5A1 Gene and Risk of the Anterior Cruciate Ligament Rupture.

Collagen alpha-1(V) chain, encoded by the COL5A1 gene, plays a crucial role in abundant fibrillar collagens supporting many tissues in the body containing type I collagen and appears to regulate the association between heterotypic fibers composed of both type I and type V collagen occurring among others in muscles, tendons and ligaments. Taking this fact into consideration we decided to examine the association between COL5A1 rs12722 and rs13946 polymorphisms, individually and as inferred haplotypes, with anterior cruciate ligament rupture risk (ACLR) in professional soccer players. A total of 134 male professional soccer players with surgically diagnosed primary anterior cruciate ligament ruptures and 211 apparently healthy male professional soccer players, who were without any self-reported history of ligament or tendon injury, were included in the study. Both the cases and the healthy controls were recruited from the same soccer teams, of a similar age category, and had a comparable level of exposure to anterior cruciate ligament injury. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA MiniprepKit. All samples were genotyped for the rs12722 and rs13946 polymorphisms using a Rotor-Gene realtime polymerase chain reaction. Statistically significant differences in the genotype frequencies for the COL5A1 rs13946 polymorphisms in dominant modes of inheritance occurred (p = 0.039). Statistically significant differences were documented only in the dominant model under the representation tendency of the C-C haplotype in the ACLR group compared to controls (p = 0.038). Our results suggest that variation in the COL5A1 gene may be one of the non-modifiable factors associated with the ACL injury in professional soccer players. The C-C rs12722-rs13946 haplotype provides a protective effect against the ACL tear.

Individual Responsiveness to Exercise-Induced Fat Loss and Improvement of Metabolic Profile in Young Women is Associated with Polymorphisms of Adrenergic Receptor Genes.

The effectiveness of physical exercise on fat loss and improvement of aerobic capacity varies considerably between individuals. A strong linkage exists between common allelic variants of the adrenergic receptor genes and weight gain, as well as changes in body composition. Therefore we aimed to check if body composition and metabolic variables were modulated by the ADRB2 (Gly16Arg and Glu27Gln), ADRB3 (Trp64Arg) and ADRA2A (rs553668 G/A) gene polymorphisms in 163 Polish sedentary women (age 19-24; body mass index (BMI) 21.7 ± 0.2 kg·m-2) involved in a 12-week aerobic training program. Only 74.8% of participants lost fat mass. On average, participants lost 5.8 (10.4)% of their relative fat mass with training (range: +28.3 to -63.6%). The improvement of VO2max was significantly greater in women who could lose their fat mass compared to women who were unsuccessful in fat loss (4.5 (5.6)% vs. 1.5 (3.8)%; p = 0.0045). The carriers of a low number (0-3) of obesity-related risk alleles (ADRB2 Gly16, ADRB2 Glu27, ADRA2A rs553668 G) were more successful in fat mass loss compared to the carriers of a high number (5-6) of risk alleles (7.7 (9.8) vs 4.0 (9.4)%, p = 0.0362). The presented results support the assumption that variation within adrenergic receptor genes contributes to interindividual changes of body composition in response to physical exercise.

The NOS3 G894T (rs1799983) and -786T/C (rs2070744) polymorphisms are associated with elite swimmer status.

Endothelial nitric oxide synthase (NOS3) generates nitric oxide in blood vessels and is involved in the regulation of vascular function, metabolism and muscle fibre type transformations. Evidence suggests that the NOS3 G894T (rs1799983) and -786T/C (rs2070744) polymorphisms are associated with athletic performance. The purpose of this study was to determine the association between the NOS3 G894T and -786T/C polymorphisms with elite swimmer status in Polish athletes. One hundred and ninety-seven Polish swimmers (104 males and 93 females), who competed in national and international events, and 379 healthy control subjects (222 males and 157 females) were recruited for this study. The swimmers were divided into two groups: short distance swimmers (SDS; n=147; 50-200 m) and long distance swimmers (LDS; n=49; more than 500 m). As expected, the frequencies of the -786T/C T allele (77.0 vs. 63.1%, p = 0.0085) and G-T haplotype (63.7 vs. 52.0, p=0.025) were significantly higher in the LDS group in comparison with controls. Compared with the -786T/C CC genotype, the chance of being a long distance swimmer was 8.49 times higher (CI=1.14-62.78, p=0.023) for the carriers of -786T/C T allele than in control subjects. On the other hand, the Asp allele frequency was significantly higher in the female SDS group compared with controls (34.3 vs. 18.5%, p=0.00043). In conclusion, our results demonstrate that the T allele and the G-T haplotype of the -786T/C and G894T polymorphisms may be beneficial for long distance swimmers.

Strength and aerobic training in overweight females in Gdansk, Poland.

We compared the effects of 16-week-training on rest metabolic rate, aerobic power, and body fat, and the post-exercise effects upon rest oxygen uptake and respiratory exchange ratio in overweight middle-aged females. Twenty nine overweight women (BMI 29.9 ± 1.2 kg*m-2) participated in training (3 days a week). The subjects were divided onto groups of aerobic (AT) and strength (ST) training. The results showed that the total body mass decrease and VO2 max increase did not differ in both groups. Decrease in waist circumference after 16 weeks was higher in the ST group. In the ST group fat-free mass increased during the first 8 weeks. Rest metabolic rate was increased significantly at 16th week compared to initial value in ST group only. Significant increase in post-exercise resting VO2 and respiratory exchange ratio at 12 and 36 h was observed after the strength training session only. Increase in rest metabolic rate and post-exercise rest energy expenditure occurred after strength training but not after aerobic training despite the similar increase in aerobic power. The effect of 8-16 weeks of strength training on body mass decrease was higher in comparison to aerobic training.

Post-Effort Changes in Activity of Traditional Diagnostic Enzymatic Markers in Football Players' Blood.

BACKGROUND: Long-term and intensive physical effort causes metabolic and biochemical adaptations for both athletic and non-athletic objectives. Knowing the importance of aerobic training in football players, the aim of this study was to evaluate changes in the activity of: creatinine kinase (CK), creatine kinase MB (CKMB), lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (HBDH), cholinesterase (ChE) and alkaline phosphatase (ALP) in response to a semi-long distance outdoor run under aerobic conditions among both female and male football players. METHODS: Sixteen participants aged 21.9±2 years (women) and 18.4±0.5 years (men), all of them voluntarily recruited football players, took part in an outdoor run, the women covering a distance of 7.4±0.3 km while men covered a distance of 10.7±1.0 km. Plasma activities of the studied enzymes were determined using an appropriate diagnostic assay kit. RESULTS: Our results indicate that total LDH activity could be a useful tool in evaluating physical fitness among athletes. We simultaneously established that ChE could not be a marker useful in assessing metabolic response to physical effort in athletes. Moreover, our results suggest that post-effort changes in ALP activity might be used to estimate early symptoms of certain vitamin deficiencies in an athlete's diet. CONCLUSIONS: We confirmed that the assessment of activity of selected traditional diagnostic enzymatic markers provides information about muscle state after physical effort.

Post-effort chances in C-reactive protein level among soccer players at the end of the training season.

Numerous literature data point out the differences in immunological parameters as a result of physical effort and the relation of those changes to the subject's fitness level. This study was aimed at the assessment of soccer players' condition and adaptation to physical effort based on the changes in C-reactive protein (CRP) blood level. C-reactive protein, total protein, and albumin plasma levels before and after 60-minute-long outdoor running were determined among 16 (8 men and 8 women) soccer players. Statistically significant increase in total blood protein level was observed in both studied groups. However, there were no statistically significant changes in albumin level in soccer players' blood. Determination of CRP showed that the exercise test caused changes in its level among both women and men; yet, statistically significant increase in CRP level was found only in women's blood. The different influence of effort on CRP plasma level may be explained by the involvement of various mechanisms in regulation of acute-phase responses in different conditions. It was found in our study that CRP level could be a valuable tool to assess the metabolic response to aerobic exercise.

Dynorphin B induces lateral asymmetric changes in feline spinal cord reflexes.

The effects of dynorphin B (an agonist of κ-opioid receptors) and naloxone (an antagonist of opioid receptors) on the field potentials (FPs) evoked in the lumbar spinal cord of spinalized cats were examined following successive stimulation of pairs of identical peripheral nerves on both sides of the body. The FPs were recorded bilaterally using microelectrodes from symmetrical sites of the gray matter between the L6 and L7 segments of the spinal cord transected at level of Th11. Significant changes (up to 75%) were registered in the areas of the initial positive components of the FPs evoked by sequential stimulation of the nn. gastrocnemius-soleus, flexor digitorum longus, and tibialis at both hind limbs; a difference between the effects of various nerves was not observed. Two-Way ANOVA analysis showed that two factors, the injection type and recording side, as well as a combination of these factors, strongly influenced the amplitudes of the FPs. Statistically significant side- and injection-dependent differences were registered in the majority of the tests. Both the directions of the changes in the FPs and their relative amplitudes were not strongly connected with a definite side of the spinal cord in different animals. Therefore, it is possible to postulate that the κ-opioid receptors are distributed inhomogeneously over the neuronal populations transmitting the peripheral afferent signals from different hind limbs, thus indicating a possible presence of the lateral asymmetry effects.