Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study.

PURPOSE: The aim of this study is to investigate the influence of the MCT1 T1470A polymorphism (rs1049434) on repeated sprint ability (RSA) and lactate accumulation after RSA testing. METHODS: Twenty-six elite Italian male football players (age: 17.7 ± 0.78 years; height: 179.2 ± 7.40 cm; weight: 72.1 ± 5.38 kg) performed RSA testing (6 × 30-m sprints with an active recovery between sprints), and lactate measurements were obtained at 1, 3, 5, 7, and 10 min post-exercise. Genotyping for the MCT1 T1470A polymorphism was performed using PCR. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium, being 42% wildtype (A/A), 46% heterozygotes (T/A), and 12% mutated homozygotes (T/T). Significant differences between genotypic groups were found in the two final sprint times of the RSA test. Under a dominant model, carriers of the major A-allele (Glu-490) in the dominant model showed a significantly lower sprint time compared to footballers with the T/T (Asp/Asp) genotype (5th Sprint time: A/A + T/A = 4.60 s vs TT = 4.97 s, 95% CI 0.07-0.67, p = 0.022; 6th Sprint: A/A + T/A = 4.56 s vs T/T = 4.87 s, 95% CI 0.05-0.57, p = 0.033). CONCLUSIONS: The T1470A (Glu490Asp) polymorphism of MCT1 was associated with RSA. Our findings suggest that the presence of the major A-allele (Glu-490) is favourable for RSA in football players.

Analysis of the PPARD Gene Expression Level Changes in Football Players in Response to the Training Cycle.

The PPARD gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including lipid metabolism in muscle cells. In this study, we assess the relationship between PPARD gene expression lipid metabolism parameters and the variation of the PPARD gene expression before (T1) and after 12 hours of training (T2) sessions in a group of football players. Peripheral blood lymphocytes were obtained from 22 football players (17.5±0.7 years, 178±0.7 cm, 68.05±9.18 kg). The PPARD gene expression, analyzed by quantitative polymerase chain reaction (qPCR), was significantly higher after T2 (p = 0.0006). Moreover, at the end of the training cycle, there was a significant decrease in relative fat tissue (FAT) (%) (p = 0.01) and absolute FAT (kg) (p = 0.01). A negative correlation was observed between absolute FAT (kg) and PPARD gene expression level in T2 (p = 0.03). The levels of cholesterol and triglyceride (TG) fractions were not significantly different (p >0.05) before and after training. No significant relationship between PPARD expression and cholesterol or TG levels was found. We found that physical training affects PPARD expression. Moreover, the negative correlation between PPARD expression and absolute FAT (kg) level may be indicative of the contribution of PPARD in metabolic adaptation to increased lipid uptake that can be used to control the body composition of athletes.

Are genes encoding proteoglycans really associated with the risk of anterior cruciate ligament rupture?

Proteoglycans are considered integral structural components of tendon and ligament and have been implicated in the resistance of compressive forces, collagen fibrillogenesis, matrix remodelling and cell signalling. Several sequence variants within genes encoding proteoglycans were recently implicated in modulating anterior cruciate ligament ruptures (ACLR). This study aimed to test the previously implicated variants in proteoglycan and vascular epithelial growth factor encoding genes with risk of ACLR in a population from Poland. A case control genetic association study was conducted using DNA samples from 143 healthy participants without a history of ACL injuries (99 male and 44 females) (CON group) and 229 surgically diagnosed ACLR participants (158 males and 71 females). All samples were genotyped for the ACAN: rs1516797, BGN: rs1042103, rs1126499, DCN: rs516115 and VEGFA: rs699947 variants. Main findings included the (i) ACAN rs1516797 G/T genotype which was underrepresented in the CON group (CON: 36%, n=52, ACLR: 49%, n=112, p=0.017, OR=1.68, 95% CI 1.09 to 2.57) when all participants were investigated and (ii) the BGN rs1042103 A allele was significantly under-represented in the male CON group compared to the male ACLR group (CON: 39%, n=78, ACLR: 49%, n=156, p=0.029, OR=1.5, 95% CI 1.05 to 2.15). Furthermore, BGN inferred haplotypes were highlighted with altered ACLR susceptibility. Although the study implicated the ACAN and BGN genes (combination of genotype, allele and haplotype) in modulating ACLR susceptibility, several differences were noted with previous published findings.

Catechol-oxide-methyltransferase (COMT rs4680:G>A) gene polymorphism does not affect analgesics' demand after elective hip replaceme.

Pain in patients with hip osteoarthritis appears long before surgery, and requires effective management as it affects patient comfort and daily activities. Therefore, the search for factors influencing response rate to analgesics is mandatory. In recent years, increasing attention has been paid to genetic factors underlying pain threshold and treatment efficacy. Polymorphic gene of catechol-oxide-methyltransferase (COMT) is a candidate gene associated with pain pathology and treatment response. The aim of the study was to evaluate association between the COMT rs4680:G>A polymorphism and demand for analgesics in patients subjected to elective hip replacement. The study included 196 patients after hip replacement surgery. Opioid demand was recorded and analgesic efficacy was scored using a four-level verbal pain intensity scale. COMT rs4680:G>A polymorphism was analysed by PCR-RFLP method. The studied COMT genotypes did not influence opioid administration in the studied patients from the day of surgery till day 6 afterwards. The distribution of the COMT rs4680:G>A in the studied subjects was as follows: GA­52.04%, AA­23.98% and GG­23.98%. It can be concluded that the COMT rs4680:G>A polymorphism is not associated with opioid demand in patients after elective hip replacement.

PGC-related gene variants and elite endurance athletic status in a Chinese cohort: a functional study.

This study aims to examine the association between proliferator-activated receptor γ (PGC)-gene family-related single nucleotide polymorphisms (SNPs) and elite endurance runners' status in a Chinese cohort, and to gain insights into the functionality of a subset of SNPs. Genotype distributions of 133 SNPs in PPARGC1A, PPARGC1B, PPRC1, TFAM, TFB1M, TFB2M, NRF1, GABPA, GABPB1, ERRα, and SIRT1 genes were compared between 235 elite Chinese (Han) endurance runners (127 women) and 504 healthy non-athletic controls (237 women). Luciferase gene reporter activity was determined in 20 SNPs. After adjusting for multiple comparisons (in which threshold P-value was set at 0.00041), no significant differences were found in allele/genotype frequencies between athletes and controls (when both sexes were analyzed either together or separately). The lowest P-value was found in PPARGC1A rs4697425 (P = 0.001 for the comparison of allele frequencies between elite female endurance runners and their gender-matched controls). However, no association (all P > 0.05) was observed for this SNP in a replication cohort from Poland (194 endurance athletes and 190 controls). Using functional genomics tool, the following SNPs were found to have functional significance: PPARGC1A rs6821591, rs12650562, rs12374310, rs4697425, rs13113110, and rs4452416; PPARGC1B rs251466 and rs17110586; and PPRC1 rs17114388 (all P < 0.001). This study found no significant association between PGC-related SNPs and elite endurance athlete status in the Chinese population, despite some SNPs showing potential functional significance and the strong biological rationale to hypothesize that this gene pathway is a candidate to influence endurance exercise capacity.

CKM gene polymorphism in Russian and Polish rowers.

Muscle-specific creatine kinase (CKMM) plays a vital role in the energy homeostasis of muscle cells. The A/G variation (rs8111989) located in the 3'-untranslated region of the CKM gene has been found to be the most relevant in terms of genetic testing in sport. The aim of the presented study was to test the hypothesis that the G allele might represent a genetic element that contributes to the improvement of endurance performance in Polish and Russian rowers. The distribution of the CKM genotypes was examined in a group of Polish and Russian athletes in comparison with non-athlete controls. There were no statistical differences between the rowers and the control groups across the CKM genotypes when Polish or Russian participants were analyzed. Based on the obtained results, it may be speculated that the CKM A/G polymorphism is not an important determinant of endurance performance level in Polish and Russian rowers. However, these results should be interpreted with caution as they can be limited by many factors.

Overrepresentation of the COL3A1 AA genotype in Polish skiers with anterior cruciate ligament injury.

Although various intrinsic and extrinsic risk factors for anterior cruciate ligament (ACL) rupture have been identified, the exact aetiology of the injury is not yet fully understood. Type III collagen is an important factor in the repair of connective tissue, and certain gene polymorphisms may impair the tensile strength. The aim of this study was to examine the association of the COL3A1 rs1800255 polymorphism with ACL rupture in Polish male recreational skiers. A total of 321 male Polish recreational skiers were recruited for this study; 138 had surgically diagnosed primary ACL ruptures (ACL-injured group) and 183 were apparently healthy male skiers (control group - CON) who had no self-reported history of ligament or tendon injury. Both groups had a comparable level of exposure to ACL injury. Genomic DNA was extracted from the oral epithelial cells. All samples were genotyped on a real-time polymerase chain reaction instrument. The genotype distribution in the ACL-injured group was significantly different than in CON (respectively: AA=10.1 vs 2.2%, AG=22.5 vs 36.1, GG=67.4 vs 61.8%; p=0.0087). The AA vs AG+GG genotype of COL3A1 (odds ratio (OR)=5.05; 95% confidence interval (CI), 1.62-15.71, p=0.003) was significantly overrepresented in the ACL-injured group compared with CON. The frequency of the A allele was higher in the ACL-injured group (21.4%) compared with CON (20.2%), but the difference was not statistically significant (p=0.72). This study revealed an association between the COL3A1 rs1800255 polymorphism and ACL ruptures in Polish skiers.

Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta (PPARD) gene is associated with elite athletic status.

Peroxisome proliferator-activated receptor delta (PPARδ; encoded by the PPARD gene) plays a role in energy metabolism and mitochondrial function. We have investigated the distribution of PPARD rs2267668, rs2016520 and rs1053049 polymorphisms, individually and in haplotype, in a cohort of 660 elite athletes which was subdivided into four different groups based on the different metabolic demands of their respective sports and 704 healthy controls. PPARD rs2016529 and rs1053049 were individually associated with overall elite athletic performance (P = 0.00002; and P = 0.0002) and also with athletes grouped as strength endurance (P = 0.00008; and P = 0.0003). Furthermore, PPARD A/C/C haplotype (rs2267668/rs2016520/rs1053049) was significantly underrepresented in all athletes and each subgroup of athletes when compared with controls (P < 0.000001), suggesting that harboring this specific haplotype is unfavorable for becoming an elite athlete. These results help to identify which genetic profiles may contribute to elite athletic performance, specifically the role of variants within the PPARD gene, and may be useful in talent identification or optimizing the response to training.

Does the A9285G Polymorphism in Collagen Type XII α1 Gene Associate with the Risk of Anterior Cruciate Ligament Ruptures?

One of the most severe injuries sustained by athletes is rupture of the anterior cruciate ligament (ACL). Recent investigations suggest that a predisposition for ACL rupture may be the result of specific genetic sequence variants. In light of this, we decided to investigate whether the COL12A1 A9285G polymorphism was associated with ACL ruptures in Polish football players. We compared genotypic and allelic frequencies of the COL12A1 A9285G polymorphism in two groups of athletes: 91 male football players (23 ± 3 years) with surgically diagnosed primary ACL ruptures who qualified for ligament reconstruction (cases) and 143 apparently healthy, male football players of the same ethnicity, a similar age category, and a comparable level of exposure to ACL injury, who were without any self-reported history of ligament or tendon injury (controls). DNA samples extracted from the oral epithelial cells were genotyped by using a real-time polymerase chain reaction (Ri-Ti-PCR) method. The genotype distribution in the cases were not different from those in controls (p = 0.70). The frequency of the G allele was lower in the cases (18.1%) but not statistically significant (p = 0.40) when compared with controls (21.3%). Our results are in contradiction to the hypothesis that the COL12A1 A9285G polymorphism is associated with a predisposition for ACL injury. However, these conclusions should be supported with more experimental studies on COL12A1 polymorphisms.

Bdkrb2 gene -9/+9 polymorphism and swimming performance.

The aim of the study was to evaluate the association between swimming performance and the -9/+9 (rs5810761) polymorphism within the BDKRB2 gene in successful competitive swimmers. Best individual swimming results expressed in FINA points achieved at short, middle and long distance events of 157 well-trained Polish swimmers were incorporated into an analysis. Athletes' genotype and allele distributions were analysed in comparison to 230 unrelated sedentary subjects who served as controls with the χ(2) test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR). The effects of genotype on swimming performance were analysed with two-way (3 x 2; genotype x gender) analysis of variance with metrical age as a covariate for each distance specialization. No statistical differences in the genotype and allele frequencies were found in long distance swimmers when compared with the total group of swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on swimming performance at short, middle or long distance, regardless of gender. The results of this study do not support the hypothesis that the BDKRB2 -9/+9 polymorphism is associated with swimming performance in Polish swimmers.

Is gnb3 c825t polymorphism associated with elite status of polish athletes?

UNLABELLED: The GNB3 gene encodes the beta 3 subunit of heterotrimeric G-proteins that are key components of intracellular signal transduction between G protein-coupled receptors (GPCR) and intracellular effectors and might be considered as a potential candidate gene for physical performance. OBJECTIVES: The aim of this study was to compare frequency distribution of the common C to T polymorphism at position 825 (C825T) of the GNB3 gene between athletes and nonathletic controls of the Polish population as well as to compare the genotype distribution and allele frequency of C825T variants within a group of athletes, i.e. between athletes of sports of different metabolic demands and competitive levels. METHODS: The study was performed in a group of 223 Polish athletes of the highest nationally competitive standard (123 endurance-oriented athletes and 100 strength/ power athletes). Control samples were prepared from 354 unrelated, sedentary volunteers. RESULTS: The χ(2) test revealed no statistical differences between the endurance-oriented athletes and the control group or between sprint/strength athletes and the control group across the GNB3 825C/T genotypes. There were no male-female genotype or allele frequency differences in controls or in either strength/power or endurance-oriented athletes. No statistically significant differences in either allele frequencies or genotype distribution were noted between the top-elite, elite or sub-elite of endurance-oriented and strength/power athletes and the control group. CONCLUSIONS: No association between elite status of Polish athletes and the GNB3 C825T polymorphic site has been found.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

Association of the 174 G/C polymorphism of the IL6 gene in Polish power-orientated athletes.

AIM: Interleukin-6 (IL6), has been called by some authors "an exercise factor" due to its pleiotropic effects during physical training. Several studies indicated that change in the guanine bases to cytosine at position -174 affects the transcription of the IL6 gene, and finally IL6 production level. The aim of this study was to perform confirmation studies to analyze the possible importance of the IL6 -174 G/C (rs1800795) polymorphism gene in Polish power-orientated athletes. METHODS: The study was carried out on two groups of men of the same Caucasian descent: 158 power-orientated athletes and 254 volunteers not involved in competitive sport. DNA was extracted from buccal cells donated by the subjects. Genotyping was carried out by polymerase chain reaction (PCR). Significance was assessed by Chi square (χ2) analysis. RESULTS: The results revealed that the frequency of the IL6 -174 GG genotype (53.16% vs. 35.82%; P=0.002) and G allele (68.67% vs. 57.87%; P=0.03) were significantly higher in the Polish power-orientated athletes compared to controls. CONCLUSION: These data suggest that the G allele could be one of the factors influencing the power-orientated sport performance. However, these conclusions should be supported with more experimental studies on other IL6 polymorphisms and other genes.

The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury.

OBJECTIVES: The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study. METHODS: A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method. RESULTS: Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher's exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test). CONCLUSIONS: The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.

Expression levels of selected cytokines and microRNAs in response to vitamin D supplementation in ultra-marathon runners.

Ultra-marathon (UM) running is an extreme endurance exercise. However, the mechanisms triggered with its practice remain unclear. While it is documented that strenuous physical activity activates immune responses and vitamin D plays a role in immune system suppression, data on the relationship between vitamin D status and cytokine profile in athletic populations are limited. To analyse the relative mRNA expression levels of selected pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-17, TNF-α), COX-2, vitamin D receptor and abundance of selected inflammatory microRNAs (Hsa-miR-21, -miR-146a, -miR-150, -miR-155, -miR-222, -miR-223) before and after a 100 km race in amateur runners in the presence or absence of vitamin D supplementation. Twenty runners aged 36-40years were divided into two groups: with and without vitamin D3 supplementation (10,000units daily). Blood samples were collected before and 12 h after the UM. The mRNA expression levels of selected cytokines, COX-2 and VDR in peripheral blood and abundance of serum exosomal miRNAs were investigated using q-RT-PCR. After UM, the significant up-regulation of TNF-α and hsa-miR-155 and down-regulation of IL-1ß were observed in the group with vitamin D supplementation. In its absence, hsa-miR-155 and -miR-223 were significantly up-regulated. Additionally, a reverse correlation was observed between IL-6 expression level and abundance of hsa-miR-155 and -miR-223 in both groups. No statistical differences were noted when the other miRNAs and genes were examined in the groups and at the time points. The UM-induced mRNA expression pattern of pro-inflammatory cytokines could be influenced by vitamin D supplementation and/or miRNA.

The angiotensin converting enzyme gene I/D polymorphism in Polish rowers.

Angiotensin converting enzyme gene (ACE) is the most frequent investigated gene in the context of genetic conditioning of sports-predispositions. Product of this gene is a key-element in the renin-angiotensin system responsible for the regulation of blood pressure. In this study DNA polymorphism in the ACE gene was studied in Polish rowers in order to examine the hypothesis that ACE genotype is associated with athletes performance. Fifty-five male Polish rowers including Olympic and World champions were recruited for this study. Control samples were prepared from 115 unrelated volunteers. PCR amplification of the insertion (I) or deletion (D) fragment of ACE gene was performed. Genotype distribution and allele frequencies were determined by genotype and gene counting. Significance was assessed by chi2 analysis. ACE genotype distributions amongst subjects and controls were in Hardy-Weinberg equilibrium. Compared with controls, the frequency of I allele differ significantly from that found in rower's group: 56.3% vs. 44.3%, (P=0.038) and ACE genotype frequency amongst the whole athletes group (30.9% II, 50.9% ID, 18.2% DD) was also different from expected values (control group 19.1% II, 50.4% ID, 30.4% DD; P=0.039). This data confirm a positive association of the I allele of ACE gene with endurance performance.

SOD2 gene polymorphism and muscle damage markers in elite athletes.

Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events.

The GABPB1 gene A/G polymorphism in Polish rowers.

Nuclear respiratory factor 2 (NRF2), also referred to as the GA-binding protein (GABP) transcription factor, is a key transcriptional activator of many nuclear genes which encode a wide range of mitochondrial enzymes. The variants of the GABPB1 gene encoding the beta1 subunit of NRF2 protein have been associated with physical performance, particularly endurance. The aim of this study was to confirm the possible importance of the A/G polymorphism (rs7181866) in intron 3 of the GABPB1 gene in Polish rowers. The study was carried out on 55 Polish rowers and sedentary individuals, to evaluate the possible relationships between genotype and physical performance. DNA was extracted from buccal cells donated by the subjects. Genotyping was carried out by PCR-RFLP. The results revealed that the frequency of the GABPB1 A/G genotype (89.09% AA; 10.91% AG, 0% GG; vs. 97.69% AA; 2.31% AG; 0.00% GG) %; P = 0.012) and G allele (5.50% vs. 1.17%; P = 0.014) was significantly higher in the rowers compared to controls. The results suggest that the GABPB1 gene can be taken into consideration as a genetic marker in endurance athletes. However, these conclusions should be supported with more experimental studies on other GABPB1 polymorphisms and other genes in elite endurance athletes.